2-(Poly-substituted aryl)-6-amino-5-halo-4-pyrimidinecarboxylic acids and their use as herbicides

ABSTRACT

6-Amino-5-halo-4-pyrimidinecarboxylic acids having poly-substituted aryl substituents in the 2-position, and their amine and acid derivatives, are potent herbicides demonstrating a broad spectrum of weed control.

This application claims the benefit of U.S. Provisional Application Ser.No. 60/758,671 filed on Jan. 13, 2006.

BACKGROUND OF THE INVENTION

This invention relates to certain novel 2-(poly-substitutedaryl)-6-amino-5-halo-4-pyrimidinecarboxylates and their derivatives andto the use of these compounds as herbicides.

A number of pyrimidinecarboxylic acids and their pesticidal propertieshave been described in the art. WO 2005/063721 A1 discloses a genus of2-substituted-6-amino-4-pyrimidinecarboxylic acids and their derivativesand their use as herbicides. It has now been discovered that certainparticular subclasses of the genus disclosed in '721 have greatlyimproved herbicidal activity and selectivity.

SUMMARY OF THE INVENTION

It has now been found that certain 2-(poly-substitutedaryl)-6-amino-5-halo-4-pyrimidinecarboxylic acids and their derivativesare superior herbicides with a broad spectrum of weed control againstwoody plants, grasses and sedges as well as broadleafs and withexcellent crop selectivity. The compounds further possess excellenttoxicological or environmental profiles.

The invention includes compounds of Formula I:

wherein

Q represents a halogen;

R₁ and R₂ independently represent H, C₁-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆alkynyl, hydroxy, C₁-C₆ alkoxy, amino, C₁-C₆ acyl, C₁-C₆ carboalkoxy,C₁-C₆ alkylcarbamyl, C₁-C₆ alkylsulfonyl, C₁-C₆ trialkylsilyl or C₁-C₆dialkyl phosphonyl or R₁ and R₂ taken together with N represent a 5- or6-membered saturated ring; and

Ar represents a polysubstituted aryl group selected from the groupconsisting ofa)

wherein

W₁ represents F or Cl;

X₁ represents C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkylthio, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkylthio or —NR₃R₄;

Y₁ represents halogen or C₁-C₄ haloalkyl or, when X₁ and Y₁ are takentogether, represents —O(CH₂)_(n)O— wherein n=1 or 2; and

R₃ and R₄ independently represent H or C₁-C₄ alkyl;b)

wherein

W₂ represents F or Cl;

X₂ represents C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkylthio, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkylthio or —NR₃R₄;

Y₂ represents halogen or C₁-C₄ haloalkyl or, when X₂ and Y₂ are takentogether, represents —O(CH₂)_(n)O— wherein n=1 or 2; and

R₃ and R₄ independently represent H or C₁-C₄ alkyl; andc)

wherein

Y₃ represents halogen or C₁-C₄ haloalkyl or, when Y₃ and Z₃ are takentogether, represents —O(CH₂)_(n)O— wherein n=1 or 2;

Z₃ represents C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkylthio, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkylthio or —NR₃R₄; and

R₃ and R₄ independently represent H or C₁-C₄ alkyl; and agriculturallyacceptable derivatives of the carboxylic acid group.

Compounds of Formula I wherein Q represents Cl and Br, wherein X₁ or X₂represent an alkoxy or —NR₃R₄, wherein Y₁, Y₂ or Y₃ represent Cl andwherein Ar represents a 2,3,4-trisubstituted phenyl or a2-fluoro-(4,5,6)-tetrasubstituted phenyl are independently preferred.

The invention includes herbicidal compositions comprising anherbicidally effective amount of a compound of Formula I andagriculturally acceptable derivatives of the carboxylic acid group inadmixture with an agriculturally acceptable adjuvant or carrier. Theinvention also includes a method of use of the compounds andcompositions of the present invention to kill or control undesirablevegetation by application of an herbicidal amount of the compound to thevegetation or to the locus of the vegetation as well as to the soilprior to emergence of the vegetation.

DETAILED DESCRIPTION OF THE INVENTION

The herbicidal compounds of the present invention are derivatives of6-amino-5-halo-4-pyrimidinecarboxylic acids of the formula:

wherein

Q represents a halogen; and

Ar represents a polysubstituted aryl group selected from the groupconsisting ofa)

wherein

W₁ represents F or Cl;

X₁ represents C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkylthio, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkylthio or —NR₃R₄;

Y₁ represents halogen or C₁-C₄ haloalkyl or, when X₁ and Y₁ are takentogether, represents —O(CH₂)_(n)O— wherein n=1 or 2; and

R₃ and R₄ independently represent H or C₁-C₄ alkyl;b)

wherein

-   -   W₂ represents F or Cl;    -   X₂ represents C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkylthio, C₁-C₄        haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkylthio or —NR₃R₄;

Y₂ represents halogen or C₁-C₄ haloalkyl or, when X₂ and Y₂ are takentogether, represents —O(CH₂)_(n)O— wherein n=1 or 2; and

R₃ and R₄ independently represent H or C₁-C₄ alkyl; andc)

wherein

Y₃ represents halogen or C₁-C₄ haloalkyl or, when Y₃ and Z₃ are takentogether, represents —O(CH₂)_(n)O— wherein n=1 or 2;

Z₃ represents C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkylthio, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkylthio or —NR₃R₄; and

R₃ and R4 independently represent H or C₁-C₄ alkyl.

These compounds are characterized by possessing a halogen in the5-position and a tri- or tetra-substituted aryl group in the 2-positionof the pyrimidine ring. Preferred substituted aryl groups include2,3,4-trisubstituted phenyl and 2-fluoro-(4,5,6)-tetrasubstituted phenylgroups.

The amino group at the 6-position of the pyrimidine ring can beunsubstituted or substituted with one or more C₁-C₆ alkyl, C₃-C₆alkenyl, C₃-C₆ alkynyl, hydroxy, C₁-C₆ alkoxy or amino substituents. Theamino group can be further derivatized as an amide, a carbamate, a urea,a sulfonamide, a silylamine or a phosphoramidate. Such derivatives arecapable of breaking down into the amine. An unsubstituted amino group orone substituted with one or two alkyl substituents is preferred.

The carboxylic acids of Formula I are believed to be the compounds thatactually kill or control undesirable vegetation and are typicallypreferred. Analogs of these compounds in which the acid group of thepyrimidine carboxylic acid is derivatized to form a related substituentthat can be transformed within plants or the environment to an acidgroup possess essentially the same herbicidal effect and are within thescope of the invention. Therefore, an “agriculturally acceptablederivative”, when used to describe the carboxylic acid functionality atthe 4-position, is defined as any salt, ester, acylhydrazide, imidate,thioimidate, amidine, amide, orthoester, acylcyanide, acyl halide,thioester, thionoester, dithiolester, nitrile or any other acidderivative well known in the art which (a) does not substantially affectthe herbicidal activity of the active ingredient, i.e., the2-aryl-6-amino-5-halo-4-pyrimidinecarboxylic acid, and (b) is or can behydrolyzed, oxidized or metabolized in plants or soil to the4-pyrimidinecarboxylic acid of Formula I that, depending upon the pH, isin the dissociated or the undissociated form. The preferredagriculturally acceptable derivatives of the carboxylic acid areagriculturally acceptable salts, esters and amides. Likewise, an“agriculturally acceptable derivative”, when used to describe the aminefunctionality at the 6-position, is defined as any salt, silylamine,phosphorylamine, phosphinimine, phosphoramidate, sulfonamide,sulfilimine, sulfoximine, aminal, hemiaminal, amide, thioamide,carbamate, thiocarbamate, amidine, urea, imine, nitro, nitroso, azide,or any other nitrogen containing derivative well known in the art which(a) does not substantially affect the herbicidal activity of the activeingredient, i.e., the 2-aryl-6-amino-5-halo-4-pyrimidinecarboxylic acid,and (b) is or can be hydrolyzed in plants or soil to a free amine ofFormula I. N-Oxides which are also capable of breaking into the parentpyrimidine of Formula I are also covered by the scope of this invention.

Suitable salts include those derived from alkali or alkaline earthmetals and those derived from ammonia and amines. Preferred cationsinclude sodium, potassium, magnesium, and aminium cations of theformula:R₅R₆R₇NH⁺wherein R₅, R₆, and R₇ each, independently represents hydrogen or C₁-C₁₂alkyl, C₃-C₁₂ alkenyl or C₃-C₁₂ alkynyl, each of which is optionallysubstituted by one or more hydroxy, C₁-C₄ alkoxy, C₁-C₄ alkylthio orphenyl groups, provided that R₅, R₆, and R₇ are sterically compatible.Additionally, any two of R₅, R₆, and R₇ together may represent analiphatic difunctional moiety containing 1 to 12 carbon atoms and up totwo oxygen or sulfur atoms. Salts of the compounds of Formula I can beprepared by treatment of compounds of Formula I with a metal hydroxide,such as sodium hydroxide, or an amine, such as ammonia, trimethylamine,diethanolamine, 2-methylthiopropylamine, bisallylamine,2-butoxyethylamine, morpholine, cyclododecylamine, or benzylamine. Aminesalts are often preferred forms of the compounds of Formula I becausethey are water-soluble and lend themselves to the preparation ofdesirable aqueous based herbicidal compositions.

Suitable esters include those derived from C₁-C₁₂ alkyl, C₃-C₁₂ alkenylor C₃-C₁₂ alkynyl alcohols, such as methanol, iso-propanol, butanol,2-ethylhexanol, butoxyethanol, methoxypropanol, allyl alcohol, propargylalcohol or cyclohexanol. Esters can be prepared by coupling of the4-pyrimidine carboxylic acids with the alcohol using any number ofsuitable activating agents such as those used for peptide couplings suchas dicyclohexylcarbodiimide (DCC) or carbonyl diimidazole (CDI), byreacting the corresponding acid chloride of a 4-pyrimidinecarboxylicacid of Formula I with an appropriate alcohol, by reacting thecorresponding 4-pyrimidinecarboxylic acid of Formula I with anappropriate alcohol in the presence of an acid catalyst or bytransesterification. Suitable amides include those derived from ammoniaor from C₁-C₁₂ alkyl, C₃-C₁₂ alkenyl or C₃-C₁₂ alkynyl mono- ordi-substituted amines, such as but not limited to dimethylamine,diethanolamine, 2-methylthiopropylamine, bisallylamine,2-butoxyethylamine, cyclododecylamine, benzylamine or cyclic or aromaticamines with or without additional heteroatoms such as but not limited toaziridine, azetidine, pyrrolidine, pyrrole, imidazole, tetrazole ormorpholine. Amides can be prepared by reacting the corresponding4-pyrimidinecarboxylic acid chloride, mixed anhydride, or carboxylicester of Formula I with ammonia or an appropriate amine.

The terms “alkyl”, “alkenyl” and “alkynyl”, as well as derivative termssuch as “alkoxy”, “acyl”, “alkylthio” and “alkylsulfonyl”, as usedherein, include within their scope straight chain, branched chain andcyclic moieties. The terms “alkenyl” and “alkynyl” are intended toinclude one or more unsaturated bonds.

The term “aryl”, as well as derivative terms such as “aryloxy”, refersto a phenyl.

Unless specifically limited otherwise, the term “halogen” includingderivative terms such as “halo” refers to fluorine, chlorine, bromine,and iodine.

The terms “haloalkyl” and “haloalkoxy” refer to alkyl and alkoxy groupssubstituted with from 1 to the maximum possible number of halogen atoms.

The compounds of Formula I can be made using well-known chemicalprocedures. The required starting materials are commercially availableor readily synthesized utilizing standard procedures. In the followingsynthesis schemes, the methyl esters of Formula I are shown as thetarget compounds and are depicted as Formula IA (see Scheme 1).Compounds of Formula I can be prepared from compounds of Formula IA bythe method illustrated in Example 37.

As shown in Scheme 1, the 2-aryl-6-amino-5-halo-4-pyrimidine-carboxylicacid esters of Formula IA can be made from compounds of Formula II byreaction with a halogenating reagent such as N-bromosuccinimide in asolvent such as chloroform or with1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2,2,2]-octanebis(tetrafluoroborate) (F-TEDA; SELECTFLUOR™ fluorinating agent) in asolvent such as acetonitrile. The method of Scheme 1 is illustrated inExamples 33 and 34.

As shown in Scheme 2, the 2-aryl-6-amino-4-pyrimidinecarboxylic acidesters of Formula IA (Q₁=halogen) as well as compounds of Formula II(Q₁=H) can be prepared by reaction of an appropriately substitutedpyrimidine of Formula III with a facile leaving group L, and anorganometallic compound of type IV in an inert solvent in the presenceof a transition metal catalyst.

In this case Q₁ can be hydrogen or a halogen; L can be chlorine,bromine, iodine or trifluoromethanesulfonate; M can be tri-(C₁-C₄alkyl)tin or B(OR₈)(OR₉), where R₈ and R₉ are independently of oneanother, hydrogen, C₁-C₆ alkyl, or when taken together form an ethyleneor propylene group; and “Catalyst” can be a transition metal catalyst,in particular a palladium catalyst such asbis(triphenylphosphine)palladium(II) dichloride. The method of Scheme 2is illustrated in Examples 31 and 32.

Alternatively, as shown in Scheme 3, the2-aryl-6-amino-5-halo-4-pyrimidinecarboxylic acid esters of Formula IAcan be prepared from appropriately substituted type V compoundspossessing a facile leaving group in the 2-position by reaction with anorganometallic compound of type IV in an inert solvent in the presenceof a transition metal catalyst; followed by oxidation of theintermediate thioether VI to either sulfoxide or sulfone; followed byreaction with various amines (VII). In this case, Q is a halogen; R₁₀can be an alkyl or aryl group; L can be chlorine, bromine, iodo ortrifluoromethanesulfonate; M can be tri-(C₁-C₄ alkyl)tin or B(OR₈)(OR₉),where R₈ and R₉ are independently of one another, hydrogen, C₁-C₆ alkyl,or when taken together form an ethylene or propylene group; and“Catalyst” can be a transition metal catalyst, in particular a palladiumcatalyst such as bis(triphenylphosphine)palladium(II) dichloride. Themethod of Scheme 3 is illustrated in Examples 27 and 28.

Alternatively, as shown in Scheme 4, the2-aryl-6-amino-5-halo-4-pyrimidinecarboxylic acid esters of Formula IAcan be prepared from appropriately substituted type VIII compoundssubstituted with a metal in the

2-position by reaction with an aryl compound of type IX in an inertsolvent in the presence of a transition metal catalyst; followed byoxidation of the intermediate thioether X to either sulfoxide orsulfone; followed by reaction with various amines (VII). In this case, Qis a halogen; R₁₀ can be an alkyl or aryl group; L can be chlorine,bromine, iodine or trifluoromethanesulfonate; M can be tri-(C₁-C₄alkyl)tin; and “Catalyst” can be a transition metal catalyst, inparticular a palladium catalyst suchbis(triphenylphosphine)palladium(II)dichloride. The method of Scheme 4is illustrated in Examples 29 and 30.

The coupling of III+IV, V+IV, and VIII+IX may, where appropriate, befollowed by reactions on either ring to obtain further derivatives ofthe compounds of Formula IA.

As shown in Scheme 5, appropriately substituted pyrimidines of Formula mwhere Q₁ is a halogen and L is chloro or bromo can be obtained byreaction of pyrimidine XI (Q₁ is a halogen and L is chloro or bromo)with amines of type VII. Also shown in Scheme 5, appropriatelysubstituted pyrimidines of Formula V where Q₁ is halogen; R₁₀ is analkyl or aryl group; and L is chloro or bromo can be easily obtained byreaction of pyrimidine XI (Q₁ is halogen and L is chloro or bromo) withthiolate salts of type XII in solvent system consisting of a mixture ofbenzene and water.

Also shown in Scheme 5, appropriately substituted pyrimidines of FormulaIII where Q₁ is a hydrogen and L is chloro or bromo can be prepared byreaction of pyrimidines of Formula XI (Q₁ is a hydrogen and L is chloroor bromo) with thiolate salts of type XII in a solvent system consistingof a mixture of benzene and water; followed by oxidation of theintermediate thioether XIII; followed by reaction with amines of typeVII.

Finally shown in Scheme 5, appropriately substituted pyrimidines ofFormula VIII where Q₁ is a halogen; R₁₀ is an alkyl or aryl group; and Mis trimethyltin can be made by reaction of V (Q₁ is a halogen and L ischloro or bromo) with hexamethylditin in an inert solvent such asdioxane in the presence of a transition metal catalyst such asbis(triphenylphosphine)palladium(II) dichloride. The methods of Scheme 5are illustrated in Examples 21-26.

As shown in Scheme 6, appropriately substituted pyrimidines of FormulaXI where Q₁ is hydrogen or halogen and L is chloro or bromo can beprepared from compounds of Formula XIV (Q₁ is hydrogen or chloro, see H.Gershon, J. Org. Chem. 1962, 27, 3507-3510 for preparation) by reactionwith reagents such as phosphorous oxychloride or phosphorous oxybromide.The reaction can be run neat or in the presence of a solvent such assulfolane. The method of Scheme 6 is illustrated in Example 20.

For other methods to prepare compounds of Formula I, see WO 2005/063721A1.

It is recognized that some reagents and reaction conditions describedabove for preparing compounds of Formula I may not be compatible withcertain functionalitites present in the intermediates. In theseinstances, the incorporation of protection/deprotection sequences orfunctional group interconversions into the synthesis will aid inobtaining the desired products. The use and choice of the protectiongroups will be apparent to one skilled in chemical synthesis.

One skilled in the art will recognize that, in some cases, after theintroduction of a given reagent as it is depicted in any individualscheme, it may be necessary to perform additional routine syntheticsteps not described in detail to complete the synthesis of compounds ofFormula I. One skilled in the art will also recognize that it maynecessary to perform a combination of the steps illustrated in the aboveschemes in an order other than that implied by the particular sequencepresented to prepare the compounds of Formula I.

Finally, one skilled in the art will also recognize that compounds ofFormula I and the intermediates described herein can be subjected tovarious electrophilic, nucleophilic, radical, organometallic, oxidation,and reduction reactions to add substituents or modify existingsubstituents.

The compounds of Formula I have been found to be useful as pre-emergenceand post-emergence herbicides. They can be employed at non-selective(higher) rates of application to control a broad spectrum of thevegetation in an area or at lower rates of application for the selectivecontrol of undesirable vegetation. Areas of application include pastureand rangelands, roadsides and rights of way, power lines and anyindustrial areas where control of undesirable vegetation is desirable.Another use is the control of unwanted vegetation in crops such as corn,rice and cereals. They can also be used to control undesirablevegetation in tree crops such as citrus, apple, rubber, oil palm,forestry and others. It is usually preferred to employ the compoundspostemergence. It is further usually preferred to use the compounds tocontrol a wide spectrum of woody plants, broadleaf and grass weeds, andsedges. Use of the compounds to control undesirable vegetation inestablished crops is especially indicated. While each of the2-aryl-6-amino-5-halo-4-pyrimidinecarboxylate compounds encompassed byFormula I is within the scope of the invention, the degree of herbicidalactivity, the crop selectivity, and the spectrum of weed controlobtained varies depending upon the substituents present. An appropriatecompound for any specific herbicidal utility can be identified by usingthe information presented herein and routine testing.

The term herbicide is used herein to mean an active ingredient thatkills, controls or otherwise adversely modifies the growth of plants. Anherbicidally effective or vegetation controlling amount is an amount ofactive ingredient which causes an adversely modifying effect andincludes deviations from natural development, killing, regulation,desiccation, retardation, and the like. The terms plants and vegetationinclude germinant seeds, emerging seedlings and established vegetation.

Herbicidal activity is exhibited by the compounds of the presentinvention when they are applied directly to the plant or to the locus ofthe plant at any stage of growth or before planting or emergence. Theeffect observed depends upon the plant species to be controlled, thestage of growth of the plant, the application parameters of dilution andspray drop size, the particle size of solid components, theenvironmental conditions at the time of use, the specific compoundemployed, the specific adjuvants and carriers employed, the soil type,and the like, as well as the amount of chemical applied. These and otherfactors can be adjusted as is known in the art to promote non-selectiveor selective herbicidal action. Generally, it is preferred to apply thecompounds of Formula I postemergence to relatively immature undesirablevegetation to achieve the maximum control of weeds.

Application rates of about 1 to about 1,000 g/Ha are generally employedin postemergence operations; for preemergence applications, rates ofabout 10 to about 2,000 g/Ha are generally employed. The higher ratesdesignated generally give non-selective control of a broad variety ofundesirable vegetation. The lower rates typically give selective controland can be employed in the locus of crops.

The herbicidal compounds of the present invention are often applied inconjunction with one or more other herbicides to control a wider varietyof undesirable vegetation. When used in conjunction with otherherbicides, the presently claimed compounds can be formulated with theother herbicide or herbicides, tank mixed with the other herbicide orherbicides or applied sequentially with the other herbicide orherbicides. Some of the herbicides that can be employed in conjunctionwith the compounds of the present invention include: amide herbicidessuch as allidochlor, beflubutamid, benzadox, benzipram, bromobutide,cafenstrole, CDEA, chlorthiamid, cyprazole, dimethenamid,dimethenamid-P, diphenamid, epronaz, etnipromid, fentrazamide, flupoxam,fomesafen, halosafen, isocarbamid, isoxaben, napropamide, naptalam,pethoxamid, propyzamide, quinonamid and tebutam; anilide herbicides suchas chloranocryl, cisanilide, clomeprop, cypromid, diflufenican,etobenzanid, fenasulam, flufenacet, flufenican, mefenacet, mefluidide,metarnifop, monalide, naproanilide, pentanochlor, picolinafen andpropanil; arylalanine herbicides such as benzoylprop, flamprop andflamprop-M; chloroacetanilide herbicides such as acetochlor, alachlor,butachlor, butenachlor, delachlor, diethatyl, dimethachlor, metazachlor,metolachlor, S-metolachlor, pretilachlor, propachlor, propisochlor,prynachlor, terbuchlor, thenylchlor and xylachlor; sulfonanilideherbicides such as benzofluor, perfluidone, pyrimisulfan and profluazol;sulfonamide herbicides such as asulam, carbasulam, fenasulam andoryzalin; antibiotic herbicides such as bilanafos; benzoic acidherbicides such as chloramben, dicamba, 2,3,6-TBA and tricamba;pyrimidinyloxybenzoic acid herbicides such as bispyribac andpyriminobac; pyrimidinylthiobenzoic acid herbicides such as pyrithiobac;phthalic acid herbicides such as chlorthal; picolinic acid herbicidessuch as aminopyralid, clopyralid and picloram; quinolinecarboxylic acidherbicides such as quinclorac and quinmerac; arsenical herbicides suchas cacodylic acid, CMA, DSMA, hexaflurate, MAA, MAMA, MSMA, potassiumarsenite and sodium arsenite; benzoylcyclohexanedione herbicides such asmesotrione, sulcotrione, tefuryltrione and tembotrione; benzofuranylalkylsulfonate herbicides such as benfuresate and ethofumesate;carbamate herbicides such as asulam, carboxazole chlorprocarb,dichlormate, fenasulam, karbutilate and terbucarb; carbanilateherbicides such as barban, BCPC, carbasulam, carbetamide, CEPC,chlorbufam, chlorpropham, CPPC, desmedipham, phenisopham, phenmedipham,phenmedipham-ethyl, propham and swep; cyclohexene oxime herbicides suchas alloxydim, butroxydim, clethodim, cloproxydim, cycloxydim,profoxydim, sethoxydim, tepraloxydim and tralkoxydim;cyclopropylisoxazole herbicides such as isoxachlortole and isoxaflutole;dicarboximide herbicides such as benzfendizone, cinidon-ethyl, flumezin,flumiclorac, flumioxazin and flumipropyn; dinitroaniline herbicides suchas benfluralin, butralin, dinitramine, ethalfluralin, fluchloralin,isopropalin, methalpropalin, nitralin, oryzalin, pendimethalin,prodiamine, profluralin and trifluralin; dinitrophenol herbicides suchas dinofenate, dinoprop, dinosam, dinoseb, dinoterb, DNOC, etinofen andmedinoterb; diphenyl ether herbicides such as ethoxyfen; nitrophenylether herbicides such as acifluorfen, aclonifen, bifenox,chlomethoxyfen, chlornitrofen, etnipromid, fluorodifen, fluoroglycofen,fluoronitrofen, fomesafen, furyloxyfen, halosafen, lactofen, nitrofen,nitrofluorfen and oxyfluorfen; dithiocarbamate herbicides such asdazomet and metam; halogenated aliphatic herbicides such as alorac,chloropon, dalapon, flupropanate, hexachloroacetone, iodomethane, methylbromide, monochloroacetic acid, SMA and TCA; imidazolinone herbicidessuch as imazamethabenz, imazamox, imazapic, imazapyr, imazaquin andimazethapyr; inorganic herbicides such as ammonium sulfamate, borax,calcium chlorate, copper sulfate, ferrous sulfate, potassium azide,potassium cyanate, sodium azide, sodium chlorate and sulfuric acid;nitrile herbicides such as bromobonil, bromoxynil, chloroxynil,dichlobenil, iodobonil, ioxynil and pyraclonil; organophosphorusherbicides such as amiprofos-methyl, anilofos, bensulide, bilanafos,butamifos, 2,4-DEP, DMPA, EBEP, fosamine, glufosinate, glyphosate andpiperophos; phenoxy herbicides such as bromofenoxim, clomeprop, 2,4-DEB,2,4-DEP, difenopenten, disul, erbon, etnipromid, fenteracol andtrifopsime; phenoxyacetic herbicides such as 4-CPA, 2,4-D, 3,4-DA, MCPA,MCPA-thioethyl and 2,4,5-T; phenoxybutyric herbicides such as 4-CPB,2,4-DB, 3,4-DB, MCPB and 2,4,5-TB; phenoxypropionic herbicides such ascloprop, 4-CPP, dichlorprop, dichlorprop-P, 3,4-DP, fenoprop, mecopropand mecoprop-P; aryloxyphenoxypropionic herbicides such as chlorazifop,clodinafop, clofop, cyhalofop, diclofop, fenoxaprop, fenoxaprop-P,fenthiaprop, fluazifop, fluazifop-P, haloxyfop, haloxyfop-P,isoxapyrifop, metamifop, propaquizafop, quizalofop, quizalofop-P andtrifop; phenylenediamine herbicides such as dinitramine and prodiamine;pyrazolyl herbicides such as benzofenap, pyrazolynate, pyrasulfotole,pyrazoxyfen, pyroxasulfone and topramezone; pyrazolylphenyl herbicidessuch as fluazolate and pyraflufen; pyridazine herbicides such ascredazine, pyridafol and pyridate; pyridazinone herbicides such asbrompyrazon, chloridazon, dimidazon, flufenpyr, metflurazon,norflurazon, oxapyrazon and pydanon; pyridine herbicides such asaminopyralid, cliodinate, clopyralid, dithiopyr, fluroxypyr, haloxydine,picloram, picolinafen, pyriclor, thiazopyr and triclopyr;pyrimidinediamine herbicides such as iprymidam and tioclorim; quaternaryammonium herbicides such as cyperquat, diethamquat, difenzoquat, diquat,morfamquat and paraquat; thiocarbamate herbicides such as butylate,cycloate, di-allate, EPTC, esprocarb, ethiolate, isopolinate,methiobencarb, molinate, orbencarb, pebulate, prosulfocarb,pyributicarb, sulfallate, thiobencarb, tiocarbazil, tri-allate andvernolate; thiocarbonate herbicides such as dimexano, EXD and proxan;thiourea herbicides such as methiuron; triazine herbicides such asdipropetryn, triaziflam and trihydroxytriazine; chlorotriazineherbicides such as atrazine, chlorazine, cyanazine, cyprazine,eglinazine, ipazine, mesoprazine, procyazine, proglinazine, propazine,sebuthylazine, simazine, terbuthylazine and trietazine; methoxytriazineherbicides such as atraton, methometon, prometon, secbumeton, simetonand terbumeton; methylthiotriazine herbicides such as ametryn,aziprotryne, cyanatryn, desmetryn, dimethametryn, methoprotryne,prometryn, simetryn and terbutryn; triazinone herbicides such asametridione, amibuzin, hexazinone, isomethiozin, metamitron andmetribuzin; triazole herbicides such as amitrole, cafenstrole, epronazand flupoxam; triazolone herbicides such as amicarbazone, bencarbazone,carfentrazone, flucarbazone, propoxycarbazone, sulfentrazone andthiencarbazone-methyl; triazolopyrimidine herbicides such ascloransulam, diclosulam, florasulam, flumetsulam, metosulam, penoxsulamand pyroxsulam; uracil herbicides such as butafenacil, bromacil,flupropacil, isocil, lenacil and terbacil; 3-phenyluracils; ureaherbicides such as benzthiazuron, cumyluron, cycluron, dichloralurea,diflufenzopyr, isonoruron, isouron, methabenzthiazuron, monisouron andnoruron; phenylurea herbicides such as anisuron, buturon, chlorbromuron,chloreturon, chlorotoluron, chloroxuron, daimuron, difenoxuron,dimefuron, diuron, fenuron, fluometuron, fluothiuron, isoproturon,linuron, methiuron, methyldymron, metobenzuron, metobromuron, metoxuron,monolinuron, monuron, neburon, parafluron, phenobenzuron, siduron,tetrafluron and thidiazuron; pyrimidinylsulfonylurea herbicides such asamidosulfuron, azimsulfuron, bensulfuron, chlorimuron, cyclosulfamuron,ethoxysulfuron, flazasulfuron, flucetosulfuron, flupyrsulfuron,foramsulfuron, halosulfuron, imazosulfuron, mesosulfuron, nicosulfuron,orthosulfamuron, oxasulfuron, primisulfuron, pyrazosulfuron,rimsulfuron, sulfometuron, sulfosulfuron and trifloxysulfuron;triazinylsulfonylurea herbicides such as chlorsulfuron, cinosulfuron,ethametsulfuron, iodosulfuron, metsulfuron, prosulfuron, thifensulfuron,triasulfuron, tribenuron, triflusulfuron and tritosulfuron;thiadiazolylurea herbicides such as buthiuron, ethidimuron, tebuthiuron,thiazafluron and thidiazuron; and unclassified herbicides such asacrolein, allyl alcohol, azafenidin, benazolin, bentazone,benzobicyclon, buthidazole, calcium cyanamide, cambendichlor,chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, cinmethylin,clomazone, CPMF, cresol, ortho-dichlorobenzene, dimepiperate, endothal,fluoromidine, fluridone, flurochloridone, flurtamone, fluthiacet,indanofan, methazole, methyl isothiocyanate, nipyraclofen, OCH,oxadiargyl, oxadiazon, oxaziclomefone, pentachlorophenol, pentoxazone,phenylmercury acetate, pinoxaden, prosulfalin, pyribenzoxim, pyriftalid,quinoclamine, rhodethanil, sulglycapin, thidiazimin, tridiphane,trimeturon, tripropindan and tritac. The herbicidal compounds of thepresent invention can, further, be used in conjunction with glyphosate,glufosinate or 2,4-D on glyphosate-tolerant, glufosinate-tolerant or2,4-D-tolerant crops. It is generally preferred to use the compounds ofthe invention in combination with herbicides that are selective for thecrop being treated and which complement the spectrum of weeds controlledby these compounds at the application rate employed. It is furthergenerally preferred to apply the compounds of the invention and othercomplementary herbicides at the same time, either as a combinationformulation or as a tank mix.

The compounds of the present invention can generally be employed incombination with known herbicide safeners, such as benoxacor,benthiocarb, brassinolide, cloquintocet (mexyl), cyometrinil, daimuron,dichlormid, dicyclonon, dimepiperate, disulfoton, fenchlorazole-ethyl,fenclorim, flurazole, fluxofenim, furilazole, isoxadifen-ethyl,mefenpyr-diethyl, MG 191, MON 4660, naphthalic anhydride (NA),oxabetrinil, R29148 and N-phenyl-sulfonylbenzoic acid amides, to enhancetheir selectivity. They can additionally be employed to controlundesirable vegetation in many crops that have been made tolerant to orresistant to them or to other herbicides by genetic manipulation or bymutation and selection. For example, corn, wheat, rice, soybean,sugarbeet, cotton, canola, and other crops that have been made tolerantor resistant to compounds that are acetolactate synthase inhibitors insensitive plants can be treated. Many glyphosate and glufosinatetolerant crops can be treated as well, alone or in combination withthese herbicides. Some crops (e.g. cotton) have been made tolerant toauxinic herbicides such as 2,4-dichlorophenoxyacetic acid. Theseherbicides may be used to treat such resistant crops or other auxintolerant crops.

While it is possible to utilize the2-aryl-6-amino-5-halo-4-pyrimidinecarboxylate compounds of Formula Idirectly as herbicides, it is preferable to use them in mixturescontaining an herbicidally effective amount of the compound along withat least one agriculturally acceptable adjuvant or carrier. Suitableadjuvants or carriers should not be phytotoxic to valuable crops,particularly at the concentrations employed in applying the compositionsfor selective weed control in the presence of crops, and should notreact chemically with the compounds of Formula I or other compositioningredients. Such mixtures can be designed for application directly toweeds or their locus or can be concentrates or formulations that arenormally diluted with additional carriers and adjuvants beforeapplication. They can be solids, such as, for example, dusts, granules,water dispersible granules, or wettable powders, or liquids, such as,for example, emulsifiable concentrates, solutions, emulsions orsuspensions.

Suitable agricultural adjuvants and carriers that are useful inpreparing the herbicidal mixtures of the invention are well known tothose skilled in the art.

Liquid carriers that can be employed include water, toluene, xylene,petroleum naphtha, crop oil, acetone, methyl ethyl ketone,cyclohexanone, trichloroethylene, perchloroethylene, ethyl acetate, amylacetate, butyl acetate, propylene glycol monomethyl ether and diethyleneglycol monomethyl ether, methanol, ethanol, isopropanol, amyl alcohol,ethylene glycol, propylene glycol, glycerine, and the like. Water isgenerally the carrier of choice for the dilution of concentrates.

Suitable solid carriers include talc, pyrophyllite clay, silica,attapulgus clay, kaolin clay, kieselguhr, chalk, diatomaceous earth,lime, calcium carbonate, bentonite clay, Fuller's earth, cotton seedhulls, wheat flour, soybean flour, pumice, wood flour, walnut shellflour, lignin, and the like.

It is usually desirable to incorporate one or more surface-active agentsinto the compositions of the present invention. Such surface-activeagents are advantageously employed in both solid and liquidcompositions, especially those designed to be diluted with carrierbefore application. The surface-active agents can be anionic, cationicor nonionic in character and can be employed as emulsifying agents,wetting agents, suspending agents, or for other purposes. Typicalsurface-active agents include salts of alkyl sulfates, such asdiethanol-ammonium lauryl sulfate; alkylarylsulfonate salts, such ascalcium dodecyl-benzenesulfonate; alkylphenol-alkylene oxide additionproducts, such as nonylphenol-C₁₈ ethoxylate; alcohol-alkylene oxideaddition products, such as tridecyl alcohol-C₁₆ ethoxylate; soaps, suchas sodium stearate; alkylnaphthalene-sulfonate salts, such as sodiumdibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts,such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such assorbitol oleate; quaternary amines, such as lauryl trimethyl-ammoniumchloride; polyethylene glycol esters of fatty acids, such aspoly-ethylene glycol stearate; block copolymers of ethylene oxide andpropylene oxide; and salts of mono and dialkyl phosphate esters.

Other adjuvants commonly used in agricultural compositions includecompatibilizing agenits, antifoam agents, sequestering agents,neutralizing agents and buffers, corrosion inhibitors, dyes, odorants,spreading agents, penetration aids, sticking agents, dispersing agents,thickening agents, freezing point depressants, antimicrobial agents, andthe like. The compositions may also contain other compatible components,for example, other herbicides, plant growth regulants, fungicides,insecticides, and the like and can be formulated with liquid fertilizersor solid, particulate fertilizer carriers such as ammonium nitrate, ureaand the like.

The concentration of the active ingredients in the herbicidalcompositions of this invention is generally from about 0.001 to about 98percent by weight. Concentrations from about 0.01 to about 90 percent byweight are often employed. In compositions designed to be employed asconcentrates, the active ingredient is generally present in aconcentration from about 5 to about 98 weight percent, preferably about10 to about 90 weight percent. Such compositions are typically dilutedwith an inert carrier, such as water, before application. The dilutedcompositions usually applied to weeds or the locus of weeds generallycontain about 0.0001 to about 1 weight percent active ingredient andpreferably contain about 0.001 to about 0.05 weight percent.

The present compositions can be applied to weeds or their locus by theuse of conventional ground or aerial dusters, sprayers, and granuleapplicators, by addition to irrigation water, and by other conventionalmeans known to those skilled in the art.

The following Examples are presented to illustrate the various aspectsof this invention and should not be construed as limitations to theclaims.

EXAMPLES 1. Preparation of 3-bromo-6-chloro-2-fluorophenol

A solution of 1-bromo-4-chloro-2-fluorobenzene (20.4 g, 0.100 mol) intetrahydrofuran (THF; 50 mL) was slowly added to lithiumdiisopropylamide (LDA; 0.125 mol) in THF (600 mL) at −50° C. Afteraddition, the solution was warmed to −20° C. and then cooled to −50° C.A solution of trimethyl borate (13.5 g, 0.130 mol) in THF (20 mL) wasadded slowly and the temperature was warmed to −20° C. The mixture wasthen cooled to −70° C. and a solution of peracetic acid (32% in aceticacid, 0.150 mol) was slowly added and the mixture was warmed to ambienttemperature. Water (250 mL) was added and the solution was extractedwith ethyl acetate (2×200 mL). The combined organic phases were driedand concentrated. The black oil was purified by column chromatography(20% ethyl acetate in hexanes) to give 3-bromo-6-chloro-2-fluorophenol(14.1 g, 0.063 mol) ¹H NMR (CDCl₃): δ 7.05 (m, 2H), 5.5 (br s, 1H).

Another phenol prepared according to the procedure of Example 1 was:

3-Bromo-2,6-dichlorophenol: mp 69-70° C.

2. Preparation of 1-bromo-4-chloro-2-fluoro-3-methoxybenzene

A heterogeneous mixture of 3-bromo-6-chloro-2-fluorophenol (14.4 g,0.064 mol), methyl iodide (13.5 g, 0.096 mol) and potassium carbonate(8.8 g, 0.064 mol) in acetonitrile (100 mL) was heated under reflux fortwo hours. The mixture was cooled, diluted with water (100 mL) andextracted with diethyl ether (2×150 mL). The combined extracts weredried and concentrated. The dark oil was purified by chromatography (5%ethyl acetate in hexanes) to give1-bromo-4-chloro-2-fluoro-3-methoxybenzene (14.8 g, 0.062 mol) ¹H NMR(CDCl₃): δ 7.20 (m, 1H), 7.10 (dd, 1 H), 4.0 (s, 3H).

Other compounds prepared according to the procedure of Example 2include:

1-Bromo-4-chloro-3-ethoxy-2-fluorobenzene: ¹H NMR (CDCl₃) δ 7.20 (m,1H), 7.10 (dd, 1H), 4.20 (q, 2H), 1.50 (t, 3H).

1-Bromo-2,4-dichloro-3-methoxybenzene: ¹H NMR (CDCl₃) δ 7.35 (d, 1H),7.15 (d, 1H), 3.95 (s, 3H).

1-Chloro-3,5-difluoro-2-methoxybenzene: GC-MS (m/z=178).

3. Preparation of 1-bromo-4-chloro-2-fluoro-5-methoxybenzene

A solution of 4-chloro-2-fluoro-5-methoxyaniline (25.0 g, 0.143 mol) in10% HBr (250 mL) was cooled to 0° C. and a solution of sodium nitrite(15.0 g, 0.218 mol) in water (20 mL) was slowly added. After addition,methylene chloride (50 mL) and cupric bromide (30.0 g, 0.244 mol) wereadded slowly. The reaction mixture was then warmed to ambienttemperature, stirred for one hour, filtered through a bed of celite, andextracted with methylene chloride (2×100 mL). The combined organicphases were dried and concentrated. Chromatography of the dark oil (5%ethyl acetate in hexanes) gave1-bromo-4-chloro-2-fluoro-5-methoxybenzene (16.6 g, 0.070 mol): ¹H NMR(CDCl₃): δ 7.20 (m, 1H), 7.05 (dd, 1H), 4.00 (s, 3H).

4. Preparation of 1-chloro-3,5-difluoro-4-iodo-2-methoxybenzene

2-Chloro-4,6-difluoroanisole (2.0 g, 11 mmol) was dissolved in 20 mLanhydrous THF and cooled to −70 to −75° C. 2.5M n-Butyl lithium inhexanes (6.7 mL, 17 mmol) was added dropwise. After stirring for 75minutes at −75° C., the mixture was treated dropwise with a solution ofiodine (5.1 g, 20 mmol) in 10 mL THF. After stirring for 20 minutes, thereaction solution was allowed to warm to 25° C. over 40 minutes. Thereaction mixture was diluted with Et₂O (50 mL) and stirred with diluteNaHSO₃ solution to destroy excess iodine. The separated aqueous phasewas extracted with 20 mL Et₂O. The combined ether phases were washedwith saturated NaCl, dried, and evaporated to give1-chloro-3,5-difluoro-4-iodo-2-methoxybenzene (3.1 g, 91% yield): mp62-64° C.; GC-MS (m/z=304).

5. Preparation of1-bromo-4-chloro-3-(2,2-difluoroethoxy)-2-fluorobenzene

A solution of 3-bromo-6-chloro-2-fluorophenol (15.4 g, 0.068 mol) indimethylformamide (DMF; 25 mL) was slowly added to a suspension ofsodium hydride (60% dispersion in mineral oil) (4.0 g, 0.10 mol) in DMF(100 mL) and the reaction mixture was stirred one hour. A solution ofmethanesulfonic acid 2,2-difluoroethyl ester (17.5 g, 0.109 mol) in DMF(10 mL) was slowly added. The resulting solution was heated at 70° C.for eighteen hours. The cooled solution was diluted with water (200 mL)and extracted with ethyl ether. The combined organic phases were driedand concentrated. The residual oil was purified by column chromatography(in hexanes) to give1-bromo-4-chloro-3-(2,2-difluoroethoxy)-2-fluorobenzene (9.0 g, 0.031mol): ¹H NMR (CDCl₃): δ 7.26 (m, 1H), 7.09 (m, 1H), 6.12 (tt, 1H), 4.30(td, 2H).

6. Preparation of 1-bromo-4-chloro-3-methylthio-2-fluorobenzene

A solution of 1-bromo-4-chloro-2-fluorobenzene (20.4 g, 0.100 mol) inTHF (50 mL) was slowly added to LDA (0.125 mol) in THF (600 mL) at −50°C. After addition, the solution was warmed to −20° C. and then cooled to−50° C. A solution of dimethyldisulfide (18.8 g, 0.20 mol) in THF (50mL) was then slowly added and the mixture was warmed to ambienttemperature. The reaction was quenched with water (200 mL), extractedwith ethyl acetate (2×150 mL), and the combined organic phases dried andconcentrated. The residual red oil was purified by chromatography (5%ethyl acetate in hexanes) to give1-bromo-4-chloro-3-methylthio-2-fluorobenzene (23.9 g, 0.094 mol): ¹HNMR (CDCl₃): δ 7.40 (m, 1H), 7.15 (dd, 1H), 2.50 (s, 3H).

7. Preparation of 1 -bromo-4-chloro-2-fluoro-3-methylbenzene

Diisopropylamine (15.2 g, 150 mmol) was dissolved in 100 mL THF and thesolution was cooled to −50° C. 2.5M n-butyl lithium (50 mL, 125 mmol)was added dropwise by addition funnel and the solution was again cooledto −50° C. 1-Bromo-4-chloro-3-fluorobenzene (20.95 g, 100 mmol) in 25 mLTHF was then slowly added to the LDA solution at −50° C. keeping thetemperature below −25° C., after which the solution was allowed to warmto −15° C. The reaction mixture was then cooled again to −60° C. andiodomethane (9.33 mL, 150 mmol) was added dropwise. The resultingsolution was allowed to warm to room temperature and concentrated undervacuum. The residue was partitioned between ethyl acetate and water. Theorganic phase was washed with water, dried, and concentrated undervacuum. The product was purified by column chromatography using hexanesas the sole solvent to yield 1-bromo-4-chloro-2-fluoro-3-methylbenzene(19.3 g, 86% yield): ¹H NMR (CDCl₃): δ 7.30 (m, 1H), 7.05 (dd, 1H), 2.35(d, 3H).

8. Preparation of 3-bromo-6-chloro-2-fluorobenzaldehyde

A solution of 1-bromo-4-chloro-2-fluorobenzene (20.4 g, 0.100 mol) inTHF (50 mL) was slowly added to LDA (0.125 mol) in THF (600 mL) at −50°C. The resulting solution was then warmed to −20° C. and cooled again to−50° C. A solution of DMF (14.6 g, 0.20 mol) in THF (50 mL) was slowlyadded and the reaction mixture was allowed to warm to room temperature.The reaction was quenched with water (250 mL) and extracted with ethylacetate (2×150 mL). The combined organic phases were dried andconcentrated. The product was recrystallized from hexane to give3-bromo-6-chloro-2-fluorobenzaldehyde (40.0 g, 0.169 mol): mp 92-93° C.

9. Preparation of 1-bromo-4-chloro-2-fluoro-3-difluoromethylbenzene

Diethylamino sulfur trifluoride (15.3 g, 0.096 mol) was added slowly toa solution of 3-bromo-6-chloro-2-fluorobenzaldehyde (7.50 g, 0.032 mol)in methylene chloride at 0° C. The resulting solution was stirred forone hour and then allowed to warm to room temperature. The reaction wascarefully quenched with a saturated solution of sodium bicarbonate inwater (100 mL) and extracted with methylene chloride (2×75 mL). Thecombined organic extracts were dried and concentrated to give1-bromo-4-chloro-2-fluoro-3-difluoro-methylbenzene (7.20 g, 0.028 mol):¹H NMR (CDCl₃): δ 7.60 (m, 1H), 7.05 (m, 1H), 7.00 (d, 1H).

10. Preparation of 2,4-dichloro-3-methoxyphenylboronic acid

To a solution of 1-bromo-2,4-dichloro-3-methoxybenzene (5.12 g, 20 mmol)in diethyl ether cooled to −70° C. was added 2.5M n-butyl lithium (8.8mL, 22 mmol) in portions keeping the temperature below −60° C. Theresulting reaction mixture was then stirred for 10 minutes beforetriisopropylborate (6.9 mL, 30 mmol) was added in portions keeping thetemperature below −60° C. The reaction mixture was then allowed to warmto room temperature and acetyl chloride (60 mmol) was added. Thereaction mixture was stirred for an hour at room temperature andconcentrated. The residue was partitioned between ethyl acetate and 1NNaOH (40 mL) and the organic phase was extracted with additional 1N NaOH(10 mL). The sodium hydroxide extracts were combined, ice was added, andthe solution was acidified to pH 3-4 with concentrated HCl. The productwas then extracted with ethyl acetate and the organic phase was driedand concentrated to yield 2,4-dichloro-3-methoxyphenylboronic acid (3.27g, 14.8 mmol): ¹H NMR (CDCl₃): δ 8.44 (br s, 2H), 7.42 (d, 1H), 7.15 (d,1H), 3.8 (s, 3H).

Other boronic acids prepared according to the procedure of Example 10include:

4-Chloro-2-fluoro-3-methylthiophenylboronic acid: ¹H NMR (CDCl₃): δ 8.39(br s, 2H), 7.49 (m, 1H), 7.35 (m, 1H), 2.43 (s, 3H).

4-Chloro-2-fluoro-3-methylphenylboronic acid:_(—) ¹H NMR (DMSO-d₆): δ8.27 (br s, 2H), 7.5-7.2 (m, 2H), 2.25 (m, 3H).

4-Chloro-3-(2,2-difluoroethoxy)-2-fluorophenylboronic acid:_(—) ¹H NMR(DMSO-d₆): δ 8.38 (br s, 2H), 7.52 (m, 1H), 7.29 (M, 1H), 6.33 (tt, 1H),4.32 (m, 2H).

11. Preparation of2-(4-chloro-2-fluoro-3-methoxyphenyl)-[1,3,2]-dioxaborinane

To a solution of 1-bromo-4-chloro-2-fluoro-3-methoxybenzene (10.4 g,0.043 mol) in diethyl ether (150 mL) at −78° C. was slowly added n-butyllithium (2.5M, 19.0 mL, 0.0475 mol), and the solution was stirred forthirty minutes. A solution of triisopropyl borate (12.0 g, 0.064 mL) inTHF (25 mL) was slowly added and the solution warmed to 0° C. Acetylchloride (10.0 g, 0.13 mol) was added. After stirring for one hour thesolution was concentrated and the solid residue was partitioned betweenethyl acetate (150 mL) and 1N sodium hydroxide (50 mL). Ice was added tothe aqueous phase that was subsequently acidified with sufficientconcentrated hydrochloric acid to obtain a pH of 2. The heterogeneousmixture was extracted with ethyl acetate (2×150 mL) and the combinedorganic phases were dried and concentrated. The resulting solid wasslurried in toluene, propane-1,3-diol (6.6 g, 0.09 mol) was added, andthe resulting mixture was heated under reflux to remove water via aDean-Stark trap. After two hours, the mixture was allowed to cool andwas concentrated under vacuum. The resulting oil was dissolved inmethylene chloride (50 mL), washed with water (25 mL), dried, andconcentrated to give2-(4-chloro-2-fluoro-3-methoxyphenyl)-[1,3,2]-dioxaborinane (6.4 g,0.062 mol): ¹H NMR (CDCl₃): δ 7.15 (m, 1H), 6.95 (dd, 1H), 4.05 (t, 4H),3.8 (s, 3H), 1.95 (t, 2H).

Other compounds prepared according to the procedure of Example 11include:

2-(4-Chloro-2-fluoro-5-methoxyphenyl)-[1,3,2]-dioxaborinane: ¹H NMR(CDCl₃): δ 7.25 (d, 1H), 7.05 (d, 1H), 4.20 (t, 4H), 4.15 (s, 3H), 2.10(t, 2H).

2-(4-Chloro-2-fluoro-3-difluoromethylphenyl)-[1,3,2]-dioxaborinane ¹HNMR (CDCl₃): δ7.75 (m, 1H), 7.15 (dd, 1H), 6.90-7.15 (t, 1H) 4.20 (t,4H), 2.05 (t, 2H).

12. Preparation of (4-chloro-3-ethoxy-2-fluorophenyl)trimethylstannane

1-Bromo-4-chloro-3-ethoxy-2-fluorobenzene: (3.55 g, 14 mmol) andhexamethylditin (5.9 g, 18 mmol) were dissolved in 25 mL p-dioxane andbis(triphenylphosphine)palladium(II) dichloride (491 mg, 0.70 mmol) wasadded. The reaction mixture was heated at 100° C. for 5 hours, allowedto cool to room temperature and concentrated. The residue was purifiedby column chromatography (0-5% ethyl acetate/hexane gradient) to yield(4-chloro-3-ethoxy-2-fluorophenyl)trimethylstannane (4.3 g, 12.7 mmol);85% pure by GC-MS m/z 338 (M⁺).

13. Preparation of 1-fluoro-2,3-methylenedioxybenzene

Alliquat 336 (methyltrioctylammonium chloride (0.63 g, 0.0016 mol),dibromomethane (40.7 g, 234.2 mmol), and water (31 mL) were placed in a500 mL 3-necked flask equipped with an addition funnel, condenser and astir bar. The addition funnel was charged with a solution of3-fluorocatechol (20.0 g, 6.1 mmol) in 5M sodium hydroxide (80 mL). Themixture in the flask was heated to reflux and the solution of thecatechol was added dropwise with good stirring over 1.5 hours. Theresulting dark mixture was heated an additional 2 hours at reflux. Aftercooling to room temperature, the reaction was diluted with methylenechloride and water. The aqueous layer was extracted with methylenechloride and the combined organic layers were dried and concentrated togive 1-fluoro-2,3-methylenedioxybenzene (14.6 g, 104.2 mmol) as a darkyellow oil: ¹H NMR (CDCl₃): δ 6.80 (m, 1H), 6.68 (m, 2H), 6.04 (s, 2H).

14. Preparation of 2-fluoro-3,4-methylenedioxyphenylboronic acid

1-Fluoro-2,3-methylenedioxybenzene (5.0 g, 35.7 mmol) was dissolved inTHF (70 mL) and the solution was cooled to −65° C. in a dry ice acetonebath. n-Butyl lithium (2.5 g, 15.7 mL, 39.3 mmol) was added to thesolution via syringe with stirring. The reaction was allowed to warm to−35° C. over 1 hour, then cooled to −65° C. and treated withtrimethylborate (4.1 g, 39.3 mmol) via syringe. The reaction was allowedto warm slowly to room temperature, quenched with 1N HCl (50 mL),stirred for 15 minutes, and then extracted with ether. The organic phasewas then extracted with 1N sodium hydroxide and this aqueous extract wasthen acidified with 1N hydrochloric acid. The acidic aqueous solutionwas then extracted with two portions of ether and these combined etherextracts were dried and concentrated to an oily solid that wastriturated with methylene chloride. The resulting solid was collected byfiltration, washed with methylene chloride, and dried to give1-fluoro-2,3-methylenedioxyphenylboronic acid (1.4 g, 7.6 mmol) as a tansolid: ¹H NMR (DMSO-d₆): δ 8.05 (br s, 2H), 7.08 (dd, 1H, J=7.8, 5.1Hz), 6.76 (d, 1H, J=7.8 Hz), 6.08 (s, 2H).

15. Preparation of 3-bromo-6-chloro-2-fluorobenzonitrile

A suspension of 3-bromo-6-chloro-2-fluorobenzaldehyde (9.0 g, 0.04 mol)and hydroxylamine-O-sulfonic acid (7.50 g, 0.07 mole) in water (300 mL)was heated at 50° C. for eighteen hours. The suspension was cooled andthe solid was collected to give 3-bromo-6-chloro-2-fluorobenzonitrile(8.8 g, 0.04 mol): ¹H NMR (CDCl₃): δ 7.75 (m, 1H), 7.25 (m, 1H).

16. Preparation of 3-bromo-2-fluoro-6-chlorobenzamide

Concentrated sulfuric acid (15 mL) was placed in a 100 mL 3-neck flaskequipped with an internal thermometer and heated to 55° C.3-Bromo-2-fluoro-6-chlorobenzonitrile (11.0 g, 47 mmol) was addedportion-wise to the acid with stirring maintaining the temperature above50° C. The dark solution was heated at 65° C. for 24 hours, allowed tocool to room temperature, poured over ice, and cautiously neutralizedwith concentrated ammonium hydroxide. The mixture was extracted with twoportions of ethyl acetate and the combined organic layers were dried andconcentrated to give 3-bromo-2-fluoro-6-chlorobenzamide (11.5 g, 45.5mmol) as a light orange solid: mp 157-158° C., ¹H NMR (CDCl₃): δ 7.54(t, 1H), 7.14 (dd, 1H), 6.03 (br s, 1H) 5.81 (br s, 1H).

17. Preparation of 3-bromo-6-chloro-2-fluoroaniline

Sodium hydroxide (4 g, 100.0 mmol) was dissolved in water (70 mL) andthe resulting solution was cooled in an ice bath and treated withbromine (4.7 g, 29.7 mmol). Solid3-bromo-2-fluoro-6-chlorobenzenecarboxamide (5.0 g, 19.9 mmol) was addedslowly with good stirring and the orange mixture was heated to refluxfor 2 hours. The cooled reaction mixture was extracted with methylenechloride and the organic phase was dried and concentrated.Recrystallization of the product from cold hexanes gave3-bromo-6-chloro-2-fluoroaniline (2.8 g, 12.6 mmol) as an off whitesolid: mp 61-62° C.: ¹H NMR (CDCl₃): δ 6.94 (dd, 1H), 6.83 (dd, 1H),4.16 (br s, 2H).

18. Preparation of N-(3-bromo-6-chloro-2-fluorophenyl)-N,N-dimethylamine

3-Bromo-6-chloro-2-fluoroaniline (2.5 g, 11.1 mmol) was dissolved in THF(25 mL) and treated with 37% formaldehyde (0.84 g, 2.1 mL, 27.8 mmol),dibutyltindichloride (0.07 g, 0.22 mmol), and phenyl silane (1.33 g,12.3 mmol). The resulting solution was then stirred at room temperatureunder nitrogen for 48 hours. The reaction mixture was concentrated undervacuum and purified by column chromatography (hexanes) to giveN-(3-bromo-6-chloro-2-fluorophenyl)-N,N-dimethylamine (2.0 g, 7.9 mmol)as an oil: ¹H NMR (CDCl₃): δ 7.19 (dd, 1H), 7.04 (dd, 1H), 2.88 (s, 3H),2.87 (s, 3H).

19. Preparation of 4-chloro-3-(dimethylamino)-2-fluorophenylboronic acid

N-(3-Bromo-6-chloro-2-fluorophenyl)-N,N-dimethylaniline (0.88 g 3.5mmol) was dissolved in ether (10 mL) and cooled to −60° C. undernitrogen. n-Butyl lithium (0.23 g, 3.6 mmol, 1.45 mL of a 2.5M solution)was added dropwise via syringe keeping the temperature under −55° C.After 0.5 hours, trimethylborate (0.40 g, 0.38 mmol) was added viasyringe and the reaction was allowed to warm to room temperature. 1N HCl(3.5 mL) was added and the mixture was stirred for 0.5 hours. Themixture was diluted with water and extracted with ether. The organicphase was dried and concentrated to give 0.75 g of a foam that wastriturated with hexanes. The resulting solid was collected by filtrationand dried to give 4-chloro-3-(dimethylamino)-2-fluorophenylboronic acid(0.5 g, 2.3 mmol) as an off-white solid. ¹H NMR (DMSO-d₆) revealed thesolid to be a mixture of what appears to be the boronic acid andanhydrides. The solid was subsequently used without further purificationor characterization.

20. Preparation of 2,6-dibromo-5-chloropyrimidine-4-carboxylic acidmethyl ester

Methyl 5-chloroorotate (33.8 g, 165 mmol, see H. Gershon, J. Org. Chem.1962, 27, 3507-3510 for preparation) and phosphorous oxybromide (100 g,349 mmol) were combined in sulfolane (200 mL). The resulting suspensionwas heated at 100-110° C. for 2 hours and then allowed to cool to roomtemperature. The cooled reaction mixture was poured onto ice and theproduct was extracted with hexane (4×150 mL). The organic extracts werecombined and concentrated to yield2,6-dibromo-5-chloropyrimidine-4-carboxylic acid methyl ester (32.0 g,58.7% yield) that was used in subsequent reactions without furtherpurification. An analytical sample was recrystallized from heptane: mp92-93° C.

21. Preparation of 2-bromo-5-chloro-6-methylthiopyrimidine-4-carboxylicacid methyl ester

An aqueous solution (15 mL) of sodium thiomethoxide (1.37 g, 19.5 mmol)was added dropwise to a solution of2,6-dibromo-5-chloro-pyrimidine-4-carboxylic acid methyl ester (4.96 g,15 mmol) in benzene (100 mL). The biphasic solution was stirred at roomtemperature for two hours at which point GC analysis indicated completeconsumption of starting material. The organic phase was washed withbrine twice, dried, and concentrated. Purification by columnchromatography yielded2-bromo-5-chloro-6-methylthiopyrimidine-4-carboxylic acid methyl ester(4.2 g, 94% yield): mp 105-106° C.

22. Preparation of5-chloro-6-methylthio-2-trimethylstannanylpyrimidine-4-carboxylic acidmethyl ester

Hexamethylditin (5.0 g, 15.3 mmol),bis(triphenylphosphine)-palladium(II) dichloride (448 mg, 0.64 mmol),and 2-bromo-5-chloro-6-methylthiopyrimidine-4-carboxylic acid methylester (3.8 g, 12.75 mmol) were combined in dioxane and heated at 100° C.for 3 hours. The reaction mixture was then allowed to cool to roomtemperature, concentrated, and the product was isolated by columnchromatography (Note: To avoid decomposition of product, column must becompleted rapidly). This process yielded5-chloro-6-methylthio-2-trimethylstannanylpyrimidine-4-carboxylic acidmethyl ester as a clear oil product (2.0 g, 41% yield): ¹H NMR (CDCl₃):δ 3.98 (s, 3 H), 2.58 (s, 3 H), 0.39 (s, 9 H).

23. Preparation of 6-amino-2,5-dichloropyrimidine-4-carboxylic acidmethyl ester

Ammonia was bubbled through a solution of2,5,6-trichloro-pyrimidine-4-carboxylic acid methyl ester (15.94 g, 66mmol, see H. Gershon, J. Org. Chem. 1962, 27, 3507-3510 for preparation)in p-dioxane (150 mL) for 30 minutes. The solvent was then removed andthe residue partitioned between ethyl acetate and water. The organicphase was dried and concentrated under vacuum. The product was purifiedby column chromatography to provide6-amino-2,5-dichloropyrimidine-4-carboxylic acid methyl ester (12.74 g,87% yield): mp 164-166° C.

24. Preparation of 2-chloro-6-methylthiopyrimidine-4-carboxylic acidmethyl ester

An aqueous solution (45 mL) of sodium thiomethoxide (4.7 g, 67 mmol) wasadded dropwise to a solution of 2,6-dichloro-pyrimidine-4-carboxylicacid methyl ester (12.5 g, 60.4 mmol) in benzene (300 mL). The biphasicsolution was stirred at room temperature for two hours at which point GCanalysis indicated complete consumption of starting material. Theorganic phase was washed with brine twice, dried, and concentrated.Purification by column chromatography yielded2-chloro-6-methylthiopyrimidine-4-carboxylic acid methyl ester (5.6 g,42.6% yield): mp 90-92° C.; ¹H NMR (CDCl₃): δ 7.78 (s, 1H), 4.00 (s,3H), 2.63 (s, 3H).

25. Preparation of 2-chloro-6-methanesulfonylpyrimidine-4-carboxylicacid methyl ester

2-Chloro-6-methylthiopyrimidine-4-carboxylic acid methyl ester (4.38 g,20 mmol) was dissolved in methylene chloride and m-chloroperoxy-benzoicacid (MCPBA; 70%) (12.3 g, 50 nmrol) was added. The reaction mixture wasstirred at room temperature for 3 days, concentrated under vacuum, andthe residue partitioned between ethyl acetate and water. The organicphase was washed with a sodium bisulfite solution, washed with a sodiumbicarbonate solution, dried, and concentrated under vacuum. The productwas purified by column chromatography (methylene chloride/ethyl acetategradient) to yield 2-chloro-6-methanesulfonylpyrimidine-4-carboxylicacid methyl ester (3.8 g, 76% yield): mp 127-129° C.: ¹H NMR (CDCl₃): δ8.56 (s, 1H), 4.09 (s, 3H), 3.34 (s, 3H).

26. Preparation of 6-amino-2-chloropyrimidine-4-carboxylic acid methylester

2-Chloro-6-methanesulfonylpyrimidine-4-carboxylic acid methyl ester (3.7g, 14.75 mmol) was dissolved in dioxane and 7N ammonia in methanol wasadded. The reaction mixture was stirred at room temperature for 3 hours,concentrated under vacuum, and the residue partitioned between ethylacetate and water. The organic phase was dried and concentrated. Theproduct was purified by column chromatography to provide6-amino-2-chloropyrimidine-4-carboxylic acid methyl ester (2.35 g, 85%yield): ¹H NMR (DMSO-d₆): δ 7.6 (br s, 1H), 7.00 (s, 1H), 3.84 (s, 3H),3.33 (s, 3H).

27. Preparation of5-chloro-2-(4-chloro-3-ethoxy-2-fluorophenyl)-6-methane-sulfonylpyrimidine-4-carboxylicacid methyl ester

2-Bromo-5-chloro-6-methylthiopyrimidine-4-carboxylic acid methyl ester(2.98 g, 10 mmol), (4-chloro-3-ethoxy-2-fluorophenyl)-trimethylstannane(3.37 g, 10 mmol), and bis(triphenylphosphine)palladium(II) dichloride(351 mg, 0.5 mmol) were combined in 20 mL N-methylpyrrolidinone andheated at 110° C. for 3 hours. The reaction mixture was allowed to coolto room temperature and was then diluted with water. The water wasdecanted from the sticky residue and the residue was washed withadditional water. The residue was purified by column chromatography(ethyl acetate/hexane gradient) and the intermediate product wascombined with 2.5 eq of MCPBA in methylene chloride and stirredovernight. The excess MCPBA was quenched by the addition of a sodiumbisulfite solution and the product was extracted with diethyl ether. Theorganic phase was washed with sodium bicarbonate solution, concentrated,and purified by column chromatography (ethyl acetate/hexane gradient). Asecond purification by column chromatography (methylene chloride only)yielded5-chloro-2-(4-chloro-3-ethoxy-2-fluorophenyl)-6-methanesulfonylpyrimidine-4-carboxylicacid methyl ester (350 mg, 8.3% yield): mp 164-166° C.

28. Preparation of6-amino-5-chloro-2-(4-chloro-3-ethoxy-2-fluorophenyl)-pyrimidine-4-carboxylicacid methyl ester (Compound 1)

5-Chloro-2-(4-chloro-3-ethoxy-2-fluorophenyl)-6-methane-sulfonylpyrimidine-4-carboxylicacid methyl ester (350 mg, 0.83 mmol) was dissolved in 10 mL p-dioxaneand 7N ammonia in methanol (0.43 mL, 3 mmol) was added. The reactionmixture was stirred at room temperature for 3 hours and thenconcentrated. The residue was partitioned between ethyl acetate andwater and the organic phase was dried and concentrated. The product waspurified by column chromatography to yield6-amino-5-chloro-2-(4-chloro-3-ethoxy-2-fluorophenyl)-pyrimidine-4-carboxylicacid methyl ester (160 mg, 54% yield): ¹H NMR (CDCl₃): δ 7.65 (dd, 1H),7.24 (dd, 1H), 5.67 (br s, 2H), 4.22 (q, 2H), 4.03 (s, 3H), 1.46 (t,3H).

29. Preparation of5-chloro-2-(4-chloro-2,6-difluoro-3-methoxyphenyl)-6-methylthiopyrimidine-4-carboxylicacid methyl ester

5-Chloro-6-methylthio-2-trimethylstannanylpyrimidine-4-carboxylic acidmethyl ester (500 mg, 1.3 mmol),1-chloro-3,5-difluoro-4-iodo-2-methoxybenzene (475 mg, 1.6 mmol) andPd[P(o-Tol)₃]Cl₂ (100 mg, 0.13 mmol) were combined in 3 mL deaerated1,2-dichloroethane. The resulting solution was heated at 130° C. for 20minutes in a CEM Discover microwave. This process was repeated withanother 500 mg sample of the stannane. The solvent was removed from thecombined reaction mixtures and the residue was chromatographed on a 50mm×250 mm YMC AQ column using 75% acetonitrile-25% 0.1% v/v H₃PO₄ toyield5-chloro-2-(4-chloro-2,6-difluoro-3-methoxyphenyl)-6-methylthio-pyrimidine-4-carboxylicacid methyl ester (153 mg, 15% yield): mp 144-146° C.; MS: m/z=394.

30. Preparation of6-amino-5-chloro-2-(4-chloro-2,6-difluoro-3-methoxy-phenyl)pyrimidine-4-carboxylicacid methyl ester (Compound 2)

5-chloro-2-(4-chloro-2,6-difluoro-3-methoxyphenyl)-6-methylthiopyrimidine-4-carboxylicacid methyl ester (150 mg, 0.38 mmol) was dissolved in 10 mL methylenechloride and treated with 70% MCPBA (240 mg, 0.95 mmol). After stirringfor 2 hours an additional 100 mg of MCPBA was added and stirring wascontinued for 18 hours. The mixture was stirred with 5 mL 10% NaHSO₃solution for 20 minutes. The separated organic phase was washed with 10%NaHCO₃ solution (5 mL), washed with water (5 mL), dried, andconcentrated. The residue was dissolved in 10 mL 0.5M ammonia in dioxaneand stirred at 25° C. for 20 hours and then concentrated under vacuum.The residue was taken up in 10 mL ethyl acetate, washed with 10 mL ofwater, washed with 5 mL of brine, dried, and concentrated to give6-amino-5-chloro-2-(4-chloro-2,6-difluoro-3-methoxyphenyl)pyrimidine-4-carboxylicacid methyl ester (51 mg, 37% yield): ¹H NMR (CDCl₃): δ 7.03 (dd, 1H),5.87 (br s, 2H), 4.0 (s, 3H), 3.93 (d, 3H).

31. Preparation of6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylicacid methyl ester (Compound 3)

6-Amino-2,5-dichloropyrimidine-4-carboxylic acid methyl ester (888 mg, 4mmol), 2-(4-chloro-2-fluoro-3-methoxyphenyl)-[1,3,2]-dioxaborinane (1.47g, 6 mmol), bis(triphenylphosphine)palladium(II) dichloride (280 mg, 0.4mmol), and cesium fluoride (1.21 g, 8 mmol) were combined in 8 mL of1,2-dimethoxyethane and 8 mL of water. The reaction mixture was heatedat 80° C. for 3 hours and the cooled reaction mixture was partitionedbetween ethyl acetate and water. The organic phase was washed withwater, dried, and concentrated. The product was purified by columnchromatography (ethyl acetate/hexane gradient) then purified again bycolumn chromatography (methylene chloride/ethyl acetate gradient) toyield6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxyphenyl)pyrimidine-4-carboxylicacid methyl ester (738 mg, 53.5% yield): ¹H NMR (CDCl₃): δ 7.64 (dd,1H), 7.22 (dd, 1H), 5.64 (br s, 2H), 4.01 (s, 3H), 3.99 (d, 3H).

The following compounds were prepared according to the procedure ofExample 31 utilizing either boronic acid esters or boronic acids:

6-Amino-5-chloro-2-(4-chloro-2-fluoro-3-methylthiophenyl)pyrimidine-4-carboxylicacid methyl ester (Compound 4): ¹H NMR (CDCl₃): δ 7.83 (dd, 1H), 7.33(dd, 1H), 5.71 (br s, 2H), 4.01 (s, 3H), 2.5 (d, 3H).

6-Amino-5-chloro-2-(4-chloro-2-fluoro-5-methoxyphenyl)pyrimidine-4-carboxylicacid methyl ester (Compound 5): ¹H NMR (CDCl₃): δ 7.53 (d, 1H), 7.22 (d,1H), 5.71 (br s, 2H), 4.02 (s, 3H), 3.95 (s, 3H).

6-Amino-5-chloro-2-(2,4-dichloro-3-methoxyphenyl)pyrimidine-4-carboxylicacid methyl ester (Compound 6): ¹H NMR (CDCl₃): δ 7.39 (m, 2H), 5.71 (brs, 2H), 4.02 (s, 3H), 3.95 (s, 3H).

6-Amino-5-chloro-2-(4-chloro-3-difluoromethyl-2-fluorophenyl)pyrimidine-4-carboxylicacid methyl ester (Compound 7): mp 155-157° C.

6-Amino-5-chloro-2-(4-chloro-3-dimethylamino-2-fluorophenyl)pyrimidine-4-carboxylicacid methyl ester (Compound 8): mp 143-144° C.

6-Amino-5-chloro-2-(4-fluorobenzo[1,3]dioxol-5-yl)pyrimidine-4-carboxylicacid methyl ester (Compound 9): ¹H NMR (CDCl₃): δ 7.59 (dd, 1H), 6.72(dd, 1H), 6.08 (s, 2H), 5.6 (br s, 2H), 4.03 (s, 3H).

6-Amino-5-chloro-2-[4-chloro-3-(2,2-difluoroethoxy)-2-fluorophenyl]-pyrimidine-4-carboxylicacid methyl ester (Compound 10): mp 139-141° C.

6-Amino-5-chloro-2-(4-chloro-2-fluoro-3-methylphenyl)pyrimidine-4-carboxylic acid methyl ester (Compound 11):mp 166-168° C.

32. Preparation of6-amino-2-(4-chloro-2-fluoro-3-methoxy-phenyl)-pyrimidine-4-carboxylicacid methyl ester.

6-Amino-2-chloro-pyrimidine-4-carboxylic acid methyl ester (2.25 g, 12mmol), 4-chloro-2-fluoro-3-methoxyphenylboronic acid (3.27 g, 16 mmol),and bis(triphenylphosphine)palladium(II) dichoride (842 mg, 1.2 mmol)were combined in 12 mL of dimethoxyethane and 12 mL of water. Thereaction mixture was heated at 80° C. for 2 hours and the cooledreaction mixture was partitioned between ethyl acetate and water. Theorganic phase was washed with water, dried, and concentrated undervacuum. The product was purified by column chromatography to yield6-amino-2-(4-chloro-2-fluoro-3-methoxy-phenyl)pyrimidine-4-carboxylicacid methyl ester (2.0 g, 53.5% yield): mp 188-190° C.: ¹H NMR (CDCl₃):δ 7.66 (dd, 1H), 7.22 (dd, 1H), 7.14 (s, 1H), 5.25 (br s, 2H), 4.0 (s,3H), 3.99 (s, 3H).

33. Preparation of6-amino-2-(4-chloro-2-fluoro-3-methoxy-phenyl)-5-fluoro-pyrimidine-4-carboxylicacid methyl ester (Compound 12).

6-Amino-2-(4-chloro-2-fluoro-3-methoxy-phenyl)-pyrimidine-4-carboxylicacid methyl ester (778 mg, 2.5 mmol) and F-TEDA (974 mg, 2.75 mmol) werecombined in acetonitrile and heated at reflux for 4 hours (reaction madelittle progress after 1 hour). The reaction mixture was cooled to roomtemperature and filtered. The filtrate was concentrated, purified bycolumn chromatography, and then purified a second time by preparativeHPLC to yield6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoropyrimidine-4-carboxylicacid methyl ester (26 mg, 3.2% yield): mp 200-202° C.: ¹H NMR (CDCl₃): δ7.62 (dd, 1H), 7.21 (dd, 1H), 5.40 (br s, 2H), 4.02 (s, 3H), 4.0 (d, 3H)

34. Preparation of6-amino-5-bromo-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylicacid methyl ester (Compound 13)

6-Amino-2-(4-chloro-2-fluoro-3-methoxy-phenyl)-pyrimidine-4-carboxylicacid methyl ester (778 mg, 2.5 mmol) and N-bromosuccinimide (489 mg,2.75 mmol) were combined in chloroform and heated at reflux for 12hours. The cooled reaction mixture was concentrated and the product wasisolated by column chromatography to yield6-amino-5-bromo-2-(4-chloro-2-fluoro-3-methoxyphenyl)pyrimidine-4-carboxylicacid methyl ester (752 mg, 77% yield):

mp 173-175° C.: ¹H NMR (CDCl₃): δ 7.66 (dd, 1H), 7.24 (dd, 1H), 5.73 (brs, 2H), 4.03 (s, 3H), 4.01 (d, 3H).

35. Preparation of6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methanesulfinyl-phenyl)pyrimidine-4-carboxylicacid methyl ester

6-Amino-5-chloro-2-(4-chloro-2-fluoro-3-methylthio-phenyl)pyrimidine-4-carboxylicacid methyl ester (2.4 g, 6.63 mmol) was dissolved with heating in aminimum amount of trifluoroethanol (50 mL). After allowing the reactionmixture to cool to room temperature, 30% hydrogen peroxide (3.0 mL, 26.5mmol) was added and the reaction mixture was stirred for 2 days. Anaqueous solution of sodium sulfite (10% solution) was added to quenchexcess oxidant (exotherm noted) and the reaction mixture was stirred for1 hour. Additional water was then added and the reaction mixture wasfiltered. The precipitate was found to be pure6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methanesulfinylphenyl)pyrimidine-4-carboxylicacid methyl ester (2.13 g, 85% yield): mp 256-258° C.: ¹H NMR (CDCl₃): δ8.03 (dd, 1H), 7.54 (dd, 1H), 3.92 (s, 3H), 3.13 (s, 3H).

36. Preparation of6-amino-5-chloro-2-(4-chloro-2-fluoro-3-trifluoro-methylthiophenyl)pyrimidine-4-carboxylicacid methyl ester (Compound 14)

6-Amino-5-chloro-2-(4-chloro-2-fluoro-3-methanesulfinyl-phenyl)pyrimidine-4-carboxylicacid methyl ester (378 mg, 1 mmol) was suspended in trifluoroaceticanhydride (5 mL) and the reaction mixture was heated at 60° C. in asealed tube for 3 hours. The reaction mixture was allowed to cool toroom temperature and the excess trifluoroacetic anhydride was removedunder reduced pressure. To the residue was added 40 mL of a 1:1 mixtureof triethylamine and methanol that was cooled to 0° C. The reactionmixture was immediately concentrated under vacuum and the resultingproduct redissolved in acetonitrile. To this solution was addedtrifluoromethyliodide (1.96 g, 10 mmol) condensed with a cold finger.The reaction mixture was placed in a glass sealed reaction vessel andirradiated with UV light for 15 minutes. The reaction mixture was thenconcentrated under vacuum and the residue was stirred in methanolovernight to remove the amine protecting group. The reaction mixture wasconcentrated once more and purified by column chromatography to yield6-amino-5-chloro-2-(4-chloro-2-fluoro-3-trifluoromethylthiophenyl)pyrimidine-4-carboxylicacid methyl ester (238 mg, 57% yield): mp 167-169° C.: ¹H NMR (CDCl₃): δ8.13 (dd, 1H), 7.47 (dd, 1H), 5.69 (br s, 2H), 4.02 (s, 3H).

37. Preparation of6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylicacid (Compound 15)

6-Amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylicacid methyl ester (156 mg, 0.45 mmol) was dissolved in 15 mL methanoland 1 mL of 2N sodium hydroxide (2 mmol) was added. The reaction mixturewas stirred at room temperature for 2 hours and then acidified with aslight excess of 2N HCl. The resulting solution was concentrated under anitrogen stream and several crops of crystals were collected during thisprocess yielding6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxyphenyl)pyrimidine-4-carboxylicacid (100 mg, 66.7% yield): mp 172-173° C.: ¹H NMR (DMSO-d₆): δ 8.0 (br,1H), 7.63 (dd, 1H), 7.43 (dd, 1H), 3.92 (s, 3H).

Other compounds prepared by the method of Example 37 include:

6-Amino-5-chloro-2-(4-chloro-2-fluoro-3-methylthiophenyl)pyrimidine-4-carboxylicacid (Compound 16): mp 139-141° C.

6-Amino-5-chloro-2-(4-chloro-2-fluoro-5-methoxyphenyl)pyrimidine-4-carboxylicacid (Compound 17): mp 202-204° C.

6-Amino-5-chloro-2-(2,4-dichloro-3-methoxyphenyl)pyrimidine-4-carboxylicacid (Compound 18): 139-141° C.

6-Amino-5-chloro-2-(4-chloro-3-ethoxy-2-fluorophenyl)pyrimidine-4-carboxylicacid (Compound 19): mp 132-134° C.

6-Amino-5-chloro-2-(4-chloro-2-fluoro-3-methylphenyl)pyrimidine-4-carboxylicacid (Compound 20): mp 210-212° C.

6-Amino-5-chloro-2-[4-chloro-3-(2,2-difluoroethoxy)-2-fluorophenyl]-pyrimidine-4-carboxylicacid (Compound 21): ¹H NMR (DMSO-d₆+D₂O): δ 7.7 (dd, 1H), 7.46 (dd, 1H),6.34 (tt, 1H), 4.41 (td, 2H).

6-Amino-5-chloro-2-(4-fluoro-benzo[1,3]dioxol-5-yl)pyrimidine-4-carboxylicacid (Compound 22): ¹H NMR (DMSO-d₆+D₂O): δ 7.48 (dd, 1H), 6.91 (d, 1H),8.2 (s, 2H).

6-Amino-5-chloro-2-(4-chloro-3-dimethylamino-2-fluorophenyl)pyrimidine-4-carboxylicacid (Compound 23): mp 181-183° C.

6-Amino-5-chloro-2-(4-chloro-3-difluoromethyl-2-fluorophenyl)pyrimidine-4-carboxylicacid (Compound 24): mp 166-168° C.

6-Amino-5-bromo-2-(4-chloro-2-fluoro-3-methoxyphenyl)pyrimidine-4-carboxylicacid (Compound 25) mp 173-175° C.

38. Preparation of Herbicidal Compositions

In the following illustrative compositions, parts and percentages are byweight. EMULSIFIABLE CONCENTRATES WT % Formulation A Compound 1 26.2Polyglycol 26-3 5.2 Nonionic emulsifier-(di-sec-butyl)-phenyl-poly(oxypropylene)block polymer with (oxyethylene). Thepolyoxyethelene content is about 12 moles. Witconate P12-20 (Anionicemulsifier- 5.2 calcium dodecylbenzene sulfonate- 60 wt. % active)Aromatic 100 (Xylene range aromatic solvent) 63.4 Formulation B Compound3 3.5 Sunspray 11N (paraffin oil) 40.0 Polyglycol 26-3 19.0 Oleic acid1.0 Xylene range aromatic solvent 36.5 Formulation C Compound 6 13.2Stepon C-65 25.7 Ethomeen T/25 7.7 Ethomeen T/15 18.0 Xylene rangearomatic solvent 35.4 Formulation D Compound 2 30.0 Agrimer A1-10LC(emulsifier) 3.0 N-methyl-2-pyrrolidone 67.0 Formulation E Compound 410.0 Agrimul 70-A (dispersant) 2.0 Amsul DMAP 60 (thickener) 2.0Emulsogen M (emulsifier) 8.0 Attagel 50 (suspension aid) 2.0 Crop oil76.0

These concentrates can be diluted with water to give emulsions ofsuitable concentrations for controlling weeds. WETTABLE POWDERS WT %Formulation F Compound 15 26.0 Polyglycol 26-3 2.0 Polyfon H 4.0 Zeosyl100 (Precipitated hydrated SiO₂) 17.0 Barden clay + inerts 51.0Formulation G Compound 19 62.4 Polyfon H (sodium salt of ligninsulfonate) 6.0 Sellogen HR (sodium naphthalene sulfonate) 4.0 Zeosyl 10027.6 Formulation H Compound 21 1.4 Kunigel V1 (carrier) 30.0 Stepanol MEDry (wetter) 2.0 Tosnanon GR 31A (binder) 2.0 Kaolin NK-300 Clay(filler) 64.6

The active ingredient is applied to the corresponding carriers and thenthese are mixed and ground to yield wettable powders of excellentwettability and suspension power. By diluting these wettable powderswith water it is possible to obtain suspensions of suitableconcentrations for controlling weeds. WATER DISPERSIBLE GRANULES WT %Formulation I Compound 25 26.0 Sellogen HR 4.0 Polyfon H 5.0 Zeosyl 10017.0 Kaolinite clay 48.0

The active ingredient is added to the hydrated silica, which is thenmixed with the other ingredients and ground to a powder. The powder isagglomerated with water and sieved to provide granules in the range of−10 to +60 mesh. By dispersing these granules in water it is possible toobtain suspensions of suitable concentrations for controlling weeds.GRANULES WT % Formulation J Compound 20  5.0 Celetom MP-88 95.0

The active ingredient is applied in a polar solvent such asN-methylpyrollidinone, cyclohexanone, gamma-butyrolactone, etc. to theCeletom MP 88 carrier or to other suitable carriers. The resultinggranules can be applied by hand, granule applicator, airplane, etc. inorder to control weeds. WT % Formulation K Compound 18 1.0 Polyfon H 8.0Nekal BA 77 2.0 Zinc Stearate 2.0 Barden Clay 87.0

All materials are blended and ground to a powder then water is added andthe clay mixture is stirred until a paste is formed. The mixture isextruded through a die to provide granules of proper size. Water SolubleLiquids WT % Formulation L Compound 23 3.67 Monoethanolamine pH buffer0.5 Water 95.83

The active ingredient is dissolved in an appropriate amount of water andthe additional monoethanolamine is added as a buffer. A water-solublesurfactant may be added. Other aids may be incorporated to improvephysical, chemical and/or formulation properties.

39. Evaluation of General Postemergence Herbicidal Activity

Seeds or nutlets of the desired test plant species were planted in SunGro MetroMix® 306 planting mixture, which typically has a pH of 6.0 to6.8 and an organic matter content of about 30 percent, in plastic potswith a surface area of 64 square centimeters. When required to ensuregood germination and healthy plants, a fungicide treatment and/or otherchemical or physical treatment was applied. The plants were grown for7-21 days in a greenhouse with an approximate 15 hour photoperiod whichwas maintained at about 23-29° C. during the day and 22-28° C. duringthe night. Nutrients and water were added on a regular basis andsupplemental lighting was provided with overhead metal halide 1000-Wattlamps as necessary. The plants were employed for testing when theyreached the first or second true leaf stage.

A weighed amount, determined by the highest rate to be tested, of eachtest compound was placed in a 25 mL glass vial and was dissolved in 4 mLof a 97:3 v/v (volume/volume) mixture of acetone and dimethyl sulfoxide(DMSO) to obtain concentrated stock solutions. If the test compound didnot dissolve readily, the mixture was warmed and/or sonicated. Theconcentrated stock solutions obtained were diluted with 20 mL of anaqueous mixture containing acetone, water, isopropyl alcohol, DMSO,Atplus 411F crop oil concentrate, and Triton® X-155 surfactant in a48.5:39:10:1.5:1.0:0.02 v/v ratio to obtain spray solutions containingthe highest application rates. Additional application rates wereobtained by serial dilution of 12 mL of the high rate solution into asolution containing 2 mL of 97:3 v/v (volume/volume) mixture of acetoneand dimethyl sulfoxide (DMSO) and 10 mL of an aqueous mixture containingacetone, water, isopropyl alcohol, DMSO, Atplus 411F crop oilconcentrate, and Triton X-155 surfactant in a 48.5:39:10:1.5:1.0:0.02v/v ratio to obtain 1/2X, 1/4X, 1/8X and 1/16X rates of the high rate.Compound requirements are based upon a 12 mL application volume at arate of 187 L/ha. Formulated compounds were applied to the plantmaterial with an overhead Mandel track sprayer equipped with a 8002Enozzles calibrated to deliver 187 L/ha over an application area of 0.503square meters at a spray height of 18 inches (43 cm) above the averageplant canopy height. Control plants were sprayed in the same manner withthe solvent blank.

The treated plants and control plants were placed in a greenhouse asdescribed above and watered by sub-irrigation to prevent wash-off of thetest compounds. After 14 days, the condition of the test plants ascompared with that of the untreated plants was determined visually andscored on a scale of 0 to 100 percent where 0 corresponds to no injuryand 100 corresponds to complete kill.

By applying the well-accepted probit analysis as described by J. Berksonin Journal of the American Statistical Society, 48, 565 (1953) and by D.Finney in “Probit Analysis” Cambridge University Press (1952), the abovedata can be used to calculate GR₅₀ and GR₈₀ values, which are defined asgrowth reduction factors that correspond to the effective dose ofherbicide required to kill or control 50 percent or 80 percent,respectively, of a target plant.

Some of the compounds tested, application rates employed, plant speciestested, and results are given in Table 1 and Table 2. TABLE 1Post-emergent Weed Control

% Control Rate Compound # M Q W X Y Z (g ai/ha) CHEAL ABUTH HELAN 1 OCH₃Cl F OCH₂CH₃ Cl H 140 100 100 100 3 OCH₃ Cl F OCH₃ Cl H 140 100 100 1004 OCH₃ Cl F SCH₃ Cl H 140 65 100 100 5 OCH₃ Cl F H Cl OCH₃ 140 100 95 956 OCH₃ Cl Cl OCH₃ Cl H 140 100 95 100 7 OCH₃ Cl F CF₂H Cl H 140 100 80100 8 OCH₃ Cl F N(CH₃)₂ Cl H 140 100 100 100 9 OCH₃ Cl F OCH₂O H 140 9095 100 10 OCH₃ Cl F OCH₂CF₂H Cl H 140 85 75 80 11 OCH₃ Cl F CH₃ Cl H 14095 95 100 12 OCH₃ F F OCH₃ Cl H 140 95 85 100 13 OCH₃ Br F OCH₃ Cl H 140100 100 100 14 OCH₃ Cl F SCF₃ Cl H 140 50 80 90 15 OH Cl F OCH₃ Cl H 140100 100 100 16 OH Cl F SCH₃ Cl H 140 15 85 100 17 OH Cl F H Cl OCH₃ 140100 50 80 18 OH Cl Cl OCH₃ Cl H 140 100 75 95 19 OH Cl F OCH₂CH₃ Cl H140 90 95 95 20 OH Cl F CH₃ Cl H 140 100 90 100 21 OH Cl F OCH₂CF₂H Cl H140 90 0 80 22 OH Cl F OCH₂O H 140 95 80 90 23 OH Cl F N(CH₃)₂ Cl H 140100 95 95 24 OH Cl F CF₂H Cl H 140 95 80 90 25 OH Br F OCH₃ Cl H 140 10095 100CHEAL = lambsquarter (Chenopodium album)ABUTH = velvetleaf (Abutilon theophrasti)HELAN = sunflower (Helianthus annuus)

TABLE 2 Post-emergent Weed Control

% Control Rate Compound # M Q W X Y (g ai/ha) CHEAL ABUTH HELAN 2 OCH₃Cl F OCH₃ Cl 140 100 90 100CHEAL = lambsquarter (Chenopodium album)ABUTH = velvetleaf (Abutilon theophrasti)HELAN = sunflower (Helianthus annuus)

40. Evaluation of General Preemergence Herbicidal Activity

Seeds of the desired test plant species were planted in a soil matrixprepared by mixing a loam soil (43 percent silt, 19 percent clay, and 38percent sand, with a pH of about 8.1 and an organic matter content ofabout 1.5 percent) and sand in a 70 to 30 ratio. The soil matrix wascontained in plastic pots with a surface area of 113 square centimeters.When required to ensure good germination and healthy plants, a fungicidetreatment and/or other chemical or physical treatment was applied.

A weighed amount, determined by the highest rate to be tested, of eachtest compound was placed in a 25 mL glass vial and was dissolved in 6 mLof a 97:3 v/v (volume/volume) mixture of acetone and DMSO to obtainconcentrated stock solutions. If the test compound did not dissolvereadily, the mixture was warmed and/or sonicated. The stock solutionsobtained were diluted with 18 mL of a 0.1% v/v aqueous solution ofTween® 20 surfactant to obtain spray solutions containing the highestapplication rate. Additional application rates were obtained by serialdilution of 12 mL of the high rate solution into a solution containing 3mL of 97:3 v/v mixture of acetone and DMSO and 9 mL of the 0.1% v/vaqueous solution of Tween® 20 surfactant to obtain 1/2X, 1/4X, 1/8X and1/16X rates of the high rate. Compound requirements are based upon a 12mL application volume at a rate of 187 L/ha. Formulated compounds wereapplied to the plant material with an overhead Mandel track sprayerequipped with a 8002E nozzles calibrated to deliver 187 L/ha over anapplication area of 0.503 square meters at a spray height of 18 inches(43 cm) above the soil surface. Control plants were sprayed in the samemanner with the solvent blank.

The treated pots and control pots were placed in a greenhouse maintainedwith an approximate 15 hour photoperiod and temperatures of about.23-29° C. during the day and 22-28° C. during the night. Nutrients andwater were added on a regular basis and supplemental lighting wasprovided with overhead metal halide 1000-Watt lamps as necessary. Thewater was added by top-irrigation. After 20-22 days, the condition ofthe test plants that germinated and grew as compared with that of theuntreated plants that emerged and grew was determined visually andscored on a scale of 0 to 100 percent where 0 corresponds to no injuryand 100 corresponds to complete kill or no emergence.

Some of the compounds tested, application rates employed, plant speciestested, and results are given in Table 3. TABLE 3 Pre-emergent WeedControl % Control Rate Compound # (g ai/ha) CHEAL ABUTH HELAN  2 140 90100 20  6 140 100  60 90  7 140 70 75 90 10 280 60 80  0 11 140 60 100 100  15 140 100  100  100  16 140 50 80 80 17 140 95 100   0 18 140 100 100  100  19 280 75 80 90CHEAL = lambsquarter (Chenopodium album)ABUTH = velvetleaf (Abutilon theophrasti)HELAN = sunflower (Helianthus annuus)

41. Evalution of Postemergence Herbicidal Activity in Cereal Crops

Seeds of the desired test plant species were planted in Sun GroMetroMix® 306 planting mixture, which typically has a pH of 6.0 to 6.8and an organic matter content of about 30 percent, in plastic pots witha surface area of 103.2 square centimeters. When required to ensure goodgermination and healthy plants, a fungicide treatment and/or otherchemical or physical treatment was applied. The plants were grown for7-36 days in a greenhouse with an approximate 14 hour photoperiod whichwas maintained at about 18° C. during the day and 17° C. during thenight. Nutrients and water were added on a regular basis andsupplemental lighting was provided with overhead metal halide 1000-Wattlamps as necessary. The plants were employed for testing when theyreached the second or third true leaf stage.

A weighed amount, determined by the highest rate to be tested, of eachtest compound was placed in a 25 mL glass vial and was dissolved in 8 mLof a 97:3 v/v mixture of acetone and DMSO to obtain concentrated stocksolutions. If the test compound did not dissolve readily, the mixturewas warmed and/or sonicated. The concentrated stock solutions obtainedwere diluted with 16 mL of an aqueous mixture containing acetone, water,isopropyl alcohol, DMSO, Agri-dex crop oil concentrate, and Triton® X-77surfactant in a 64.7:26.0:6.7:2.0:0.7:0.01 v/v ratio to obtain spraysolutions containing the highest application rates. Additionalapplication rates were obtained by serial dilution of 12 mL of the highrate solution into a solution containing 4 mL of 97:3 v/v mixture ofacetone and DMSO and 8 mL of an aqueous mixture containing acetone,water, isopropyl alcohol, DMSO, Agri-dex crop oil concentrate, andTriton X-77 surfactant in a 48.5:39.0:10.0:1.5:1.0:0.02 v/v ratio toobtain 1/2X, 1/4X, 1/8X and 1/16X rates of the high rate. Compoundrequirements are based upon a 12 mL application volume at a rate of 187L/ha. Formulated compounds were applied to the plant material with anoverhead Mandel track sprayer equipped with a 8002E nozzles calibratedto deliver 187 L/ha over an application area of 0.503 square meters at aspray height of 18 inches (43 cm) above average plant canopy height.Control plants were sprayed in the same manner with the blank.

The treated plants and control plants were placed in a greenhouse asdescribed above and watered by sub-irrigation to prevent wash-off of thetest compounds. After 20-22 days, the condition of the test plants ascompared with that of the untreated plants was determined visually andscored on a scale of 0 to 100 percent where 0 corresponds to no injuryand 100 corresponds to complete kill.

Some of the compounds tested, application rates employed, plant speciestested, and results are given in Table 4. TABLE 4 Post-emergent Controlof Several Key Weeds in Wheat and Barley % Control Rate Compound # (gai/ha) TRZAS HORVS GALAP LAMPU PAPRH VERPE 1 35 0 0 99 85 100 20 2 35 00 95 95 100 50 3 17.5 0 0 95 99 100 99 6 70 10  0 85 99  99 99 7 17.515  0 60 90  95 95 8 35 15  0 70 85 100 95 9 70 15  0 90 100   40 30 10 70 5 0 65 85  95 20 13  17.5 0 0 90 95 100 95TRZAS = wheat (Triticum aestivum)HORVS = barley (Hordeum vulare)GALAP = Galium aparineLAMPU = Lamium purpureumPAPRH = Papaver rhoeasVERPE = Veronica persica

42. Evaluation of Herbicidal Activity in Transplanted Paddy Rice

Weed seeds or nutlets of the desired test plant species were planted inpuddled soil (mud) prepared by mixing a non-sterilized mineral soil (28percent silt, 18 percent clay, and 54 percent sand, with a pH of about7.3 to 7.8 and an organic matter content of about 1.0 percent) and waterat a ratio of 100 kg of soil to 19 L of water. The prepared mud wasdispensed in 250 mL aliquots into 480 mL non-perforated plastic potswith a surface area of 91.6 square centimeters leaving a headspace of 3centimeters in each pot. Rice seeds were planted in Sun Gro MetroMix®306 planting mixture, which typically has a pH of 6.0 to 6.8 and anorganic matter content of about 30 percent, in plastic plug trays.Seedlings at the second or third leaf stage of growth were transplantedinto 650 mL of mud contained in 960 mL non-perforated plastic pots witha surface area of 91.6 square centimeters 4 days prior to herbicideapplication. The paddy was created by filling the 3 centimeter headspaceof the pots with water. When required to ensure good germination andhealthy plants, a fungicide treatment and/or other chemical or physicaltreatment was applied. The plants were grown for 4-14 days in agreenhouse with an approximate 14 hour photoperiod which was maintainedat about 29° C. during the day and 26° C. during the night. Nutrientswere added as Osmocote (17:6:10, N:P:K+minor nutrients) at 2 g (grams)per cup. Water was added on a regular basis to maintain the paddy flood,and supplemental lighting was provided with overhead metal halide1000-Watt lamps as necessary. The plants were employed for testing whenthey reached the second or third true leaf stage.

A weighed amount, determined by the highest rate to be tested, of eachtest compound was placed in a 120 mL glass vial and was dissolved in 20mL of acetone to obtain concentrated stock solutions. If the testcompound did not dissolve readily, the mixture was warmed and/orsonicated. The concentrated stock solutions obtained were diluted with20 mL of an aqueous mixture containing 0.01% Tween 20 (v/v). Applicationrates of 1/2X, 1/4X, 1/8X and 1/16X of the high rate were obtained byinjecting an appropriate amount of the stock solution into the aqueouslayer of the paddy. Control plants were treated in the same manner withthe solvent blank.

The treated plants and control plants were placed in a greenhouse asdescribed above and water was added as needed to maintain a paddy flood.After 20-22 days, the condition of the test plants as compared with thatof the untreated plants was determined visually and scored on a scale of0 to 100 percent where 0 corresponds to no injury and 100 corresponds tocomplete kill.

Some of the compounds tested, application rates employed, plant speciestested, and results are given in Table 5. TABLE 5 Water-injected Controlof Several Key Weeds in Rice % Control Rate Compound # (g ai/ha) ORYSASCPJU CYPDI MOOVA 1 17.5 5 50 95 100 2 70 0 20 75 100 3 17.5 0 80 99 1006 17.5 0 — 90 100 7 140 0 90 100  100 8 35 0 10 95 100 9 35 0 70 100  99 10  140 0 40 95 100 13  70 0 60 85 100ORYSA = rice (Orysa sativa var. Japonica)SCPJU = Scirpus juncoidesCYPDI = Cyperus difformisMOOVA = Monochoria vaginalis

1. A compound of the formula I

wherein Q represents a halogen; R₁ and R₂ independently represent H,C₁-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, hydroxy, C₁-C₆ alkoxy, amino,C₁-C₆ acyl, C₁-C₆ carboalkoxy, C₁-C₆ alkylcarbamyl, C₁-C₆ alkylsulfonyl,C₁-C₆ trialkylsilyl or C₁-C₆ dialkyl phosphonyl or R₁ and R₂ takentogether with N represent a 5- or 6-membered saturated ring; and Arrepresents a polysubstituted aryl group selected from the groupconsisting of a)

wherein W₁ represents F or Cl; X₁ represents C₁-C₄ alkyl, C₁-C₄ alkoxy,C₁-C₄ alkylthio, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkylthioor —NR₃R₄; Y₁ represents halogen or C₁-C₄ haloalkyl or, when X₁ and Y₁are taken together, represents —O(CH₂)_(n)O— wherein n=1 or 2; and R₃and R4 independently represent H or C₁-C₄ alkyl; b)

wherein W₂ represents F or Cl; X₂ represents C₁-C₄ alkyl, C₁-C₄ alkoxy,C₁-C₄ alkylthio, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkylthioor —NRO₃R₄; Y₂ represents halogen or C₁-C₄ haloalkyl or, when X₂ and Y₂are taken together, represents —O(CH₂)_(n)O— wherein n=1 or 2; and R₃and R₄ independently represent H or C₁-C₄ alkyl; and c)

wherein Y₃ represents halogen or C₁-C₄ haloalkyl or, when Y₃ and Z₃ aretaken together, represents —O(CH₂)_(n)O— wherein n=1 or 2; Z₃ representsC₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkylthio, C₁-C₄ haloalkyl, C₁-C₄haloalkoxy, C₁-C₄ haloalkylthio or —NR₃R₄; and R₃ and R₄ independentlyrepresent H or C₁-C₄ alkyl; and agriculturally acceptable derivatives ofthe carboxylic acid group.
 2. A compound of claim 1 in which R₁ and R₂independently represent H or C₁-C₆ alkyl.
 3. A compound of claim 1 inwhich Q represents Cl or Br.
 4. A compound of claim 1 in which Arrepresents

wherein W₁ represents F or Cl; X₁ represents C₁-C₄ alkyl, C₁-C₄ alkoxy,C₁-C₄ alkylthio, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkylthioor —NR₃R₄; Y₁ represents halogen or C₁-C₄ haloalkyl or, when X₁ and Y₁are taken together, represents —O(CH₂)_(n)O— wherein n=1 or 2; and R₃and R₄ independently represent H or C₁-C₄ alkyl.
 5. A compound of claim4 in which X₁ represents C₁-C₄ alkoxy or —NR₃R₄.
 6. A compound of claim4 in which Y₁ represents Cl.
 7. A compound of claim 1 in which Arrepresents

wherein W₂ represents F or Cl; X₂ represents C₁-C₄ alkyl, C₁-C₄ alkoxy,C₁-C₄ alkylthio, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkylthioor —NR₃R₄; Y₂ represents halogen or C₁-C₄ haloalkyl or, when X₂ and Y₂are taken together, represents —O(CH₂)_(n)O— wherein n=1 or 2; and R₃and R₄ independently represent H or C₁-C₄ alkyl.
 8. A compound of claim7 in which X₂ represents C₁-C₄ alkoxy or —NR₃R₄.
 9. A compound of claim7 in which Y₂ represents Cl.
 10. A compound of claim 1 in which Arrepresents

wherein Y₃ represents halogen, C₁-C₄ haloalkyl or, when Y₃ and Z₃ aretaken together, represents —O(CH₂)_(n)O— wherein n=1 or 2; Z₃ representsC₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ alkylthio, C₁-C₄ haloalkyl, C₁-C₄haloalkoxy, C₁-C₄ haloalkylthio or —NR₃R₄.
 11. A compound of claim 10 inwhich Z₃ represents C₁-C₄ alkoxy.
 12. A compound of claim 10 in which Y₃represents Cl.
 13. A herbicidal composition comprising a herbicidallyeffective amount of a compound of Formula I, according to claim 1, in amixture with an agriculturally acceptable adjuvant or carrier.
 14. Amethod of controlling undesirable vegetation which comprises contactingthe vegetation or the locus thereof with or applying to the soil toprevent the emergence of vegetation an herbicidally effective amount ofa compound of Formula I, according to claim 1.